6O0H

Cryo-EM structure of human ATP-citrate lyase in complex with inhibitor NDI-091143


Experimental Data Snapshot

  • Method: ELECTRON MICROSCOPY
  • Resolution: 3.67 Å
  • Aggregation State: PARTICLE 
  • Reconstruction Method: SINGLE PARTICLE 

wwPDB Validation 3D Report Full Report


This is version 1.1 of the entry. See complete history

Literature

An allosteric mechanism for potent inhibition of human ATP-citrate lyase.

Wei, J.Leit, S.Kuai, J.Therrien, E.Rafi, S.Harwood Jr., H.J.DeLaBarre, B.Tong, L.

(2019) Nature 568: 566-570

  • DOI: 10.1038/s41586-019-1094-6

  • PubMed Abstract: 
  • ATP-citrate lyase (ACLY) is a central metabolic enzyme and catalyses the ATP-dependent conversion of citrate and coenzyme A (CoA) to oxaloacetate and acetyl-CoA <sup>1-5 </sup>. The acetyl-CoA product is crucial for the metabolism of fatty acids <sup ...

    ATP-citrate lyase (ACLY) is a central metabolic enzyme and catalyses the ATP-dependent conversion of citrate and coenzyme A (CoA) to oxaloacetate and acetyl-CoA 1-5 . The acetyl-CoA product is crucial for the metabolism of fatty acids 6,7 , the biosynthesis of cholesterol 8 , and the acetylation and prenylation of proteins 9,10 . There has been considerable interest in ACLY as a target for anti-cancer drugs, because many cancer cells depend on its activity for proliferation 2,5,11 . ACLY is also a target against dyslipidaemia and hepatic steatosis, with a compound currently in phase 3 clinical trials 4,5 . Many inhibitors of ACLY have been reported, but most of them have weak activity 5 . Here we report the development of a series of low nanomolar, small-molecule inhibitors of human ACLY. We have also determined the structure of the full-length human ACLY homo-tetramer in complex with one of these inhibitors (NDI-091143) by cryo-electron microscopy, which reveals an unexpected mechanism of inhibition. The compound is located in an allosteric, mostly hydrophobic cavity next to the citrate-binding site, and requires extensive conformational changes in the enzyme that indirectly disrupt citrate binding. The observed binding mode is supported by and explains the structure-activity relationships of these compounds. This allosteric site greatly enhances the 'druggability' of ACLY and represents an attractive target for the development of new ACLY inhibitors.


    Organizational Affiliation

    Department of Bacteriology, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan wachino@med.nagoya-u.ac.jp.,Microbiology and Biotechnology, Biocenter Klein Flottbek, Ohnhorststr. 18, 22609 Hamburg, Germany.,National Institutes of Health, Institutes of Health-Johns Hopkins University Graduate Partnership Program, Bethesda, MD, 20892, USA.,Department of Cell and Systems Biology, University of Toronto, 25 Willcocks Street, Toronto, ON, M5S 3B2, Canada.,Jülich Centre for Neutron Science (JCNS) at Heinz Maier-Leibnitz Zentrum (MLZ) , Forschungszentrum Jülich GmbH , Lichtenbergstrasse 1 , 85747 Garching , Germany.,Department of Chemistry, Indian Institute of Technology Bombay, Powai, Mumbai, 400 076, India. cprao@iitb.ac.in.,Department of Chemistry, University of Copenhagen, Universitetsparken 5, Copenhagen, DK-2100, Denmark.,Department of Structural Biology, Weizmann Institute of Science, Rehovot, Israel.,Department of Chemical and Geological Sciences, University of Cagliari, Cagliari, Italy.,Wisconsin Institute for Discovery, University of Wisconsin-Madison, Madison, WI, 53706, USA. xuehua.zhong@wisc.edu.,ICREA Institució Catalana de Recerca i Estudis Avançats, Barcelona, Spain.,Department of Chemistry , John Brown University , 2000 West University Street , Siloam Springs , Arkansas 72761 , United States.,Institut für Mikrobiologie , Eidgenössiche Technische Hochschule (ETH) Zürich , Vladimir-Prelog-Weg 4 , 8093 Zürich , Switzerland.,From the Shanghai Institute of Applied Physics, Chinese Academy of Sciences, Shanghai 201800 and hejianhua@sinap.ac.cn.,Roche Pharma Research and Early Development, Therapeutic Modalities, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd, 4070 Basel, Switzerland.,Department of Chemistry and Biochemistry, 103 Chemistry and Biochemistry Building, Montana State University, Bozeman, MT, 59717, USA.,Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.,Department of Computational and Systems Biology, University of Pittsburgh, Pittsburgh, PA, 15260, USA.,Department of Chemistry and Biochemistry , New Mexico State University , Las Cruces , New Mexico 88003 , United States.,Laboratory of Genetics, University of Wisconsin-Madison, Madison, WI, 53706, USA.,Department of Physics and Astronomy and LaserLaB, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands lp212@cam.ac.uk g.j.l.wuite@vu.nl e.j.g.peterman@vu.nl.,Department of Medicine at Division of Nephrology and Hypertension, Vanderbilt University Medical Center, Nashville, TN 37232, USA.,CIBER de Enfermedades Raras (CIBERER-ISCIII), Spain.,Institute for Biochemistry, Biotechnology and Bioinformatics , Technische Universität Braunschweig , 38106 Braunschweig , Germany.,Department of Chemistry, Indian Institute of Technology Bombay, Powai, Mumbai, 400 076, India.,Division of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul, 02841, Republic of Korea; Institute of Life Science and Natural Resources, Korea University, Seoul, 02841, Republic of Korea. Electronic address: structures@korea.ac.kr.,Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003, Lisbon, Portugal. rmoreira@ff.ulisboa.pt.,Department of Biomedical & Molecular Sciences, Queen's University, Kingston, ON, Canada K7L 3N6.,Beijing Advanced Innovation Center for Structural Biology, Tsinghua-Peking Joint Center for Life Sciences, School of Life Sciences and School of Medicine, Tsinghua University, Beijing 100084, China; Technology Center for Protein Sciences, Ministry of Education Key Laboratory of Protein Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China.,Bioinformatics Facility, Centro de Biología Molecular "Severo Ochoa".,the R&D Division, Hayashibara Co., Ltd., 675-1 Fujisaki, Naka-ku, Okayama 702-8006, and.,the Department of Microbiology, University of Washington School of Medicine, Seattle, Washington 98195.,Department of Biochemistry, Vanderbilt University Medical Center, Nashville, TN 37232, USA.,Division of Biotechnology, Advanced Institute of Environment and Bioscience, College of Environmental and Bioresource Sciences, Chonbuk National University, Iksan 54596, Republic of Korea.,Department of Biological Science, Graduate School of Science, Osaka Prefecture University, 1-1 Gakuen-cho, Naka-ku, Sakai, Osaka 599-8531, Japan. Electronic address: fujii@b.s.osakafu-u.ac.jp.,Center for Inflammation Research, University of Texas Southwestern Medical Center, Dallas, TX, USA. Zhijian.Chen@UTSouthwestern.edu.,Molecular Biology of Microbial Consortia, University of Hamburg, Biocenter Klein Flottbek, Ohnhorststr. 18, 22609, Hamburg, Germany.,Departamento de Microbiología Molecular, Instituto de Biotecnología, Universidad Nacional Autónoma de México, Cuernavaca, Mexico.,Instituto de Tecnologia Química e Biológica-António Xavier, Universidade Nova de Lisboa, Avenida da República, 2780-157, Oeiras, Portugal.,From the UMR Ecologie Microbienne, CNRS, INRA, VetAgro Sup, UCBL, Université de Lyon, F-69622, Villeurbanne, Lyon, France and celine.lavire@univ-lyon1.fr.,Department of Biochemistry, University of Toronto, Toronto, ON M5S 1A8, Canada.,Advanced Photon Technology Division, Research Infrastructure Group, SR Life Science Instrumentation Unit, RIKEN/SPring-8 Center, 1-1-1 Kouto, Sayo-cho, Sayo-gun, Hyogo 679-5148, Japan.,Institute of Molecular Cell and Systems Biology, University of Glasgow, Glasgow, UK.,Graduate School of Life Sciences, Tohoku University, 2-1-1, Katahira Aoba-ku, Sendai, Miyagi, 980-8577, Japan.,Meiji Seika Pharma Co., Ltd., Yokohama, Kanagawa, Japan.,Department of Integrative Structural and Computational Biology, Scripps Research Institute, La Jolla, CA, USA. Electronic address: glander@scripps.edu.,Regional Centre for Biotechnology, NCR Biotech Science Cluster, 3rd Milestone, Faridabad-Gurgaon Expressway, Faridabad 121 001, India.,Research Complex at Harwell, Rutherford Laboratory, Didcot, England.,Julius-Maximilians-Universität Würzburg, Josef Schneider Straße 2, 97080 Würzburg, Germany. Electronic address: Bettina.boettcher@uni-wuerzburg.de.,Department of Chemistry, University of Copenhagen, Universitetsparken 5, Copenhagen, DK-2100, Denmark. Electronic address: leila@chem.ku.dk.,Department of Applied Sciences, Faculty of Health and Life Sciences, Northumbria University, Newcastle upon Tyne, UK.,From the Cancer Research UK Beatson Institute, Garscube Estate, Switchback Road, Glasgow G61 1BD, Scotland, United Kingdom and the Institute of Cancer Sciences, University of Glasgow, Glasgow G61 1BD, Scotland, United Kingdom d.huang@beatson.gla.ac.uk.,Department of Chemistry , Texas A&M University , P.O. Box 30012, College Station , Texas 77842 , United States.,Department of Bioengineering, College of Life Science, Dalian Minzu University, Dalian, 116600, Liaoning, China; Key Laboratory of Biotechnology and Bioresources Utilization (Dalian Minzu University), Ministry of Education, China. Electronic address: mikyeken@dlnu.edu.cn.,School of Life Science and Biotechnology, Dalian University of Technology, No 2 Linggong Road, Dalian, 116024, Liaoning, China.,CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China; Savaid Medical School, University of Chinese Academy of Sciences, Beijing 100049, China.,National Institute of Biological Sciences, Beijing 102206, China.,Institute for Molecular Bioscience, The University of Queensland, St. Lucia, Queensland 4072, Australia.,Institute of Pathology, Ruhr-University of Bochum, Bochum, Germany.,Department of Cell and Molecular Biology, Grand Valley State University , Allendale, Michigan 49401, United States.,Department of Biochemistry and Biophysics, Stockholm University, SE-106 91 Stockholm, Sweden. Electronic address: stenmark@dbb.su.se.,Department of Bionanotechnology, Graduate School, Hanyang University, Seoul 04763, Republic of Korea.,BIOSAXS Group, European Molecular Biology Laboratory Hamburg, D-22607 Hamburg, Germany.,South China Sea Institute of Oceanology, Chinese Academy of Sciences, Guangzhou 510301, China.,Cardiovascular Research Institute, University of California - San Francisco, San Francisco, CA 94158, USA; Department of Cellular and Molecular Pharmacology, University of California - San Francisco, San Francisco, CA 94158, USA. Electronic address: natalia.jura@ucsf.edu.,Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences , 32 West 7th Avenue, Tianjin Airport Economic Area, Tianjin 300308, China.,Structural Biology Programs, Sloan Kettering Institute, New York, New York 10065.,Istituto di Biofisica , Consiglio Nazionale delle Ricerche , 56124 Pisa , Italy.,Medical Research Council Laboratory of Molecular Biology, Cambridge, United Kingdom.,State Key Laboratory of Bio-catalysis and Enzyme Engineering, Hubei Collaborative Innovation Center for Green Transformation of Bio-Resources, School of Life Sciences, Hubei University, Wuhan 430062, China. Electronic address: guoreyting@gmail.com.,School of Chemistry and Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Parkville, Victoria, Australia.,Laboratory of Biomolecular Research, Department of Biology and Chemistry, Paul Scherrer Institute, 5232 Villigen PSI, Switzerland.,Department of Microbiology, Immunology, and Biochemistry, University of Tennessee Health Science Center, Memphis, TN, United States.,Department of Biomolecular Sciences, Weizmann Institute of Science, Rehovot, 76100, Israel.,Key Laboratory of Drug Targeting and Drug Delivery System of Ministry of Education, West China School of Pharmacy, and State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu, 610041, China. Electronic address: liguobo@scu.edu.cn.,Radcliffe Department of Medicine , Division of Cardiovascular Medicine , BHF Centre of Research Excellence , Wellcome Trust Centre for Human Genetics , Roosevelt Drive , Oxford OX3 7BN , UK.,The Department of Medical Biology , University of Melbourne , Parkville , Victoria 3052 , Australia.,Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON M5S 3E2, Canada.,Experimental Center, Technische Universität Dresden, Faculty of Medicine, Fiedlerstraße 42, 01307 Dresden, Germany; Center for Membrane & Cell Physiology, University of Virginia and Department of Molecular Physiology & Biological Physics, 480 Ray C. Hung Drive, Charlottesville, VA 22903, USA.,Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan.,Division of Gastroenterology, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, 75 Francis Street, Boston, MA, 02115, USA. rblumberg@bwh.harvard.edu.,Laboratory of Physical Chemistry of Polymers and Membranes, Ecole Polytechnique Fédérale de Lausanne (EPFL) , CH B3 495 (Bâtiment CH) Station 6, CH-1015 Lausanne, Switzerland.,Cancer Hospital, Chinese Academy of Science, Hefei, Anhui, People's Republic of China.,Department of Biochemistry and Molecular Biology/ERI BIOTECMED, Universitat de València, Dr Moliner 50, Burjassot, 46100 Valencia, Spain.,Centre for Bacterial Cell Biology, Institute for Cell and Molecular Biosciences, Newcastle University, Richardson Road, Newcastle Upon Tyne, NE4AX, UK.,Dipartimento di Scienze Chimiche , Università degli Studi di Padova and Istituto di Chimica Biomolecolare, Consiglio Nazionale delle Ricerche , 35131 Padua , Italy.,State Key Laboratory of Bio-catalysis and Enzyme Engineering, Hubei Collaborative Innovation Center for Green Transformation of Bio-Resources, School of Life Sciences, Hubei University, Wuhan 430062, China.,Department of Biochemistry and Molecular Biology, University of Chicago, Chicago, Illinois, USA.,Seattle Structural Genomics Center for Infectious Disease, Seattle, WA, USA.,Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, 1649-028 Lisbon, Portugal.,Division of Life Science, State Key Laboratory of Molecular Neuroscience, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China; Center of Systems Biology and Human Health, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China. Electronic address: mzhang@ust.hk.,Division of Cardiovascular Medicine, Department of Internal Medicine, Center for Arrhythmia Research, University of Michigan, Ann Arbor, MI, United States.,Department of Bioengineering, College of Life Science, Dalian Minzu University, Dalian, 116600, Liaoning, China; Key Laboratory of Biotechnology and Bioresources Utilization (Dalian Minzu University), Ministry of Education, China.,School of Physical and Mathematical Sciences, Nanyang Technological University, Singapore 637371, Singapore.,Division of Solid Tumor Translational Oncology, German Cancer Consortium (DKTK), partner site Essen, West German Cancer Center, University Hospital Essen, Essen, Germany.,Structural Biology, St. Jude Children's Research Hospital, Memphis, TN, United States.,Midwest Center for Structural Genomics and Structural Biology Center, Biosciences, Argonne National Laboratory, Lemont, Illinois, USA ktan@anl.gov c.welte@science.ru.nl.,Department of Biochemistry and Molecular Biology, University of British Columbia, Vancouver, BC V6T 1Z3, Canada.,Hubei Key Laboratory of Cell Homeostasis, College of Life Sciences, Wuhan University, Wuhan 430072, China.,Horikoshi Gene Selector Project, Exploratory Research for Advanced Technology (ERATO), Japan Science and Technology Corporation (JST), 5-9-6 Tokodai, Tsukuba-shi, Ibaraki 300-2635, Japan.,Department of Agricultural Chemistry, Tokyo University of Agriculture, Sakuragaoka 1-1-1, Setagaya, Tokyo, 156-8502, Japan. Electronic address: sue@nodai.ac.jp.,Institute for Cell and Molecular Biosciences, Newcastle University, Newcastle upon Tyne, UK. harry.gilbert@ncl.ac.uk.,Department of Chemistry and Biochemistry, Montana State University, Bozeman, MT 59717, USA.,Department of Chemical and Biomolecular Engineering, University of California Berkeley, Berkeley, CA, 94720, USA.,Department of Organic Chemistry, University of Debrecen, POB 400, H-4002 Debrecen, Hungary.,Department of Chemistry, Rhodes University, Grahamstown 6139, South Africa.,Department of Molecular Biosciences , The University of Texas at Austin , Austin , Texas 78712 , United States.,Atreca, Inc., Redwood City, CA 94063, USA.,Max Delbrück Center for Molecular Medicine, Kristallographie, Robert-Rössle-Strasse 10, Berlin, 13125, Germany.,Winkle College of Pharmacy, University of Cincinnati, ML 0514, 231 Albert Sabin Way, MSB 3109B, Cincinnati, OH, 45267, USA.,the Department of Biochemical Science and Technology, College of Life Science.,Cecil H. and Ida Green Center for Reproductive Biology Sciences and Division of Basic Research, Department of Obstetrics and Gynecology, Department of Biophysics, UT Southwestern Medical Center, Dallas, TX, 75390, USA. xin.liu@utsouthwestern.edu.,Burnett School of Biomedical Sciences, College of Medicine , University of Central Florida , Orlando , Florida 32827 , United States.,From the Department of Biotechnology and.,Department of Physiology, Pontificia Universidad Católica de Chile, 8331150 Santiago, Chile.,Shanghai Key Laboratory of Molecular Andrology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai 200031, China.,Istituto di Chimica del Riconoscimento Molecolare, C.N.R., Milan, Italy.,Hefei National Laboratory for Physical Science at Microscale and School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230026, People's Republic of China.,From the Department of Biochemistry, s-nair@life.illinois.edu.,Munich Center for Integrated Protein Science, 81377 München, Germany.,From the Bioconversion Group and inoue-h@aist.go.jp.,Personalized Drug Therapy Key Laboratory of Sichuan Province, Hospital of the University of Electronic Science and Technology of China and Sichuan Provincial People's Hospital, Sichuan, 610072, China.,Department of Biochemistry and Biophysics, Stockholm University, SE-106 91 Stockholm, Sweden; Science for Life Laboratory Stockholm University, Box 1031, SE-171 21 Solna, Sweden. Electronic address: gunnar@dbb.su.se.,Cardiovascular Research Institute, University of California - San Francisco, San Francisco, CA 94158, USA; Department of Cellular and Molecular Pharmacology, University of California - San Francisco, San Francisco, CA 94158, USA.,Department of Chemistry, Pukyong National University, 45 Yongso-ro, Busan 48513, Republic of Korea.,Hefei National Laboratory for Physical Science at Microscale and School of Life Science, University of Science and Technology of China, Hefei, Anhui, People's Republic of China.,Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA 91125 houk@chem.ucla.edu sbjkan@caltech.edu frances@cheme.caltech.edu.,Institute for Cell and Molecular Biosciences, Newcastle University, Newcastle upon Tyne, UK.,Hefei National Laboratory for Physical Science at Microscale and School of Life Science, University of Science and Technology of China, Hefei, Anhui, People's Republic of China xmtu@ustc.edu.cn.,European Molecular Biology Laboratory (EMBL), Hamburg Outstation, Notkestrasse 85, D-22607 Hamburg, Germany.,Department of Physics and Astronomy, University of Pittsburgh, Pittsburgh, PA, 15260, USA.,Biological Sciences West, The University of Arizona, 1041 E Lowell Street, Tucson, AZ, 85721, USA.,Dipartimento di Medicina e Chirurgia , Università di Parma , 43125 Parma , Italy.,Department of Bioengineering, College of Life Science, Dalian Minzu University, Dalian, 116600, Liaoning, China; Key Laboratory of Biotechnology and Bioresources Utilization (Dalian Minzu University), Ministry of Education, China; School of Life Science and Biotechnology, Dalian University of Technology, No 2 Linggong Road, Dalian, 116024, Liaoning, China.,Department of Biochemistry and Molecular Biology, George S. Wise Faculty of Life Sciences, Tel-Aviv University, 6997801 Ramat Aviv, Israel.,National Resource for Automated Molecular Microscopy, Simons Electron Microscopy Center, New York Structural Biology Center, New York, New York, United States of America.,Department of Biochemistry and Biotechnology, University of Thessaly, Biopolis, 41500 Larissa, Greece. Electronic address: ddleonidas@bio.uth.gr.,From the Cancer Research UK Beatson Institute, Garscube Estate, Switchback Road, Glasgow G61 1BD, Scotland, United Kingdom and the Institute of Cancer Sciences, University of Glasgow, Glasgow G61 1BD, Scotland, United Kingdom.,Seattle Structural Genomics Center for Infectious Disease, Seattle, WA, USA. jan.abendroth@ucb.com.,Vanderbilt Institute of Chemical Biology Synthesis Core, Vanderbilt University, Nashville, TN 37232-0146, USA.,Department of Cell Biology, University of Texas Southwestern Medical Center, Dallas, TX, USA. Xiaochen.Bai@UTSouthwestern.edu.,Cancer institute, the Affiliated Hospital of Qingdao University, Qingdao Cancer Institute and School of Basic Medicine, Qingdao University, 266021, Qingdao, China.,Faculty of Chemistry and Chemical Biology, TU Dortmund University, Dortmund, Germany. daniel.rauh@tu-dortmund.de stephan.hahn@rub.de jens.siveke@uk-essen.de.,Vanderbilt Institute of Chemical Biology, Vanderbilt University Medical Center, Nashville, TN 37232, USA.,Schrödinger, LLC, New York, NY, USA.,High Force Research Ltd., Bowburn North Industrial Estate, Bowburn, Durham, DH6 5PF, U.K.,Division of Biology and Bioengineering, California Institute of Technology, Pasadena, CA 91125.,German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), Heidelberg, Germany. daniel.rauh@tu-dortmund.de stephan.hahn@rub.de jens.siveke@uk-essen.de.,Department of Life Sciences and Chemistry, Jacobs University, Bremen, Germany.,Department of Materials Structure Science, School of High Energy Accelerator Science, The Graduate University for Advanced Studies (Soken-dai), 1-1 Oho, Tsukuba, Ibaraki, 305-0801, Japan.,Institut Curie, PSL Research University, CNRS, UMR3664, Equipe Labellisée Ligue contre le Cancer, F-75005, Paris, France.,Biotech Research and Innovation Centre, University of Copenhagen, DK-2200 Copenhagen, Denmark.,Department of Pharmaceutical Chemistry, University of California, San Francisco, CA 94158.,Department of Biochemistry, University of Cambridge, Sanger Building, 80 Tennis Court Road, Old Addenbrooke's Site, Cambridge CB2 1GA, UK.,Laboratory for Marine Drugs and Bioproducts of Qingdao National Laboratory for Marine Science and Technology, Qingdao, 266237, China.,Department of Physiology, School of Basic Medicine and Tongji Medical College, Huazhong University of Science and Technology, Wuhan 4030030, China; The Institute for Brain Research, Collaborative Innovation Center for Brain Science, Huazhong University of Science and Technology, Wuhan 430030, China. Electronic address: lym@hust.edu.cn.,Department of Applied Life Sciences , Niigata University of Pharmacy and Applied Life Sciences , 265-1 Higashijima , Akiha-ku, Niigata 956-8603 , Japan.,The Walter and Eliza Hall Institute of Medical Research , Parkville Victoria 3052 , Australia.,Department of Biological Sciences, King Abdulaziz University, Jeddah, Saudi Arabia.,Division of Human Biology and Epidemiology Program, Seattle, Washington, United States of America.,Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA 90095.,School of Biological Sciences, University of Essex, Wivenhoe Park, Colchester, CO4 3SQ, UK. jworrall@essex.ac.uk.,Graduate School of Pharmaceutical Sciences, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.,Department of Molecular Gastrointestinal Oncology, Ruhr-University Bochum, Bochum, Germany. daniel.rauh@tu-dortmund.de stephan.hahn@rub.de jens.siveke@uk-essen.de.,Division of Life Science, State Key Laboratory of Molecular Neuroscience, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China. Electronic address: linzhijie@ust.hk.,Laboratory of Structural Biology, Key Laboratory of Cancer Proteomics of Chinese Ministry of Health, XiangYa Hospital, Central South University, Changsha, Hunan 410008, China. yonghenc@163.com.,Wisconsin Institute for Discovery, University of Wisconsin-Madison, Madison, WI, 53706, USA.,From the Departments of Medicinal Chemistry and scottee@umich.edu.,Department of Biology, 1205 Avenue Docteur Penfield, Montréal, QC H3A 1B1, Canada. Electronic address: gary.brouhard@mcgill.ca.,From the Institute of Biological Chemistry and Core Facilities for Protein Structural Analysis, Academia Sinica, Taipei 11529 and ahjwang@gate.sinica.edu.tw.,Department of Chemistry, College of Natural Sciences, Seoul National University, Seoul, 08826, Republic of Korea.,Univ Grenoble Alpes, CEA, CNRS, IBS, 38000, Grenoble, France.,CKD Research Institute, Chong Kun Dang Pharmaceutical Corporation, Yongin, 16995, Republic of Korea.,Beijing Advanced Innovation Center for Structural Biology, School of Medicine, Tsinghua University, 100084 Beijing, China.,JAN Scientific Inc., Seattle, WA 98105.,Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Melbourne, Victoria, 3086, Australia.,Department of Chemistry and Biochemistry, University of California, Los Angeles, CA 90095; houk@chem.ucla.edu sbjkan@caltech.edu frances@cheme.caltech.edu.,Division of Respirology, Department of Medicine, Queen's University, Kingston, ON, Canada K7L 3N6.,Novartis Institutes for BioMedical Research, Inc. , 250 Massachusetts Avenue , Cambridge , Massachusetts 02139 , United States.,Medicinal Bioinformatics Center, Shanghai Jiao-Tong University School of Medicine, Shanghai, China.,Instrument Division , European Spallation Source ERIC , Box 176, S-221 00 Lund , Sweden.,State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.,Department of Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15260.,Department of Physics and Astronomy and LaserLaB, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.,Department of Microbiology and Cell Biology, Indian Institute of Science, Bangalore, India.,Department of Biophysics, Beijing Key Laboratory of Tumor Systems Biology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China.,Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America.,Department of Chemistry - BMC, Uppsala University, Box 576, SE-75123 Uppsala, Sweden.,Target Discovery Institute (TDI) , Nuffield Department of Medicine , University of Oxford , NDMRB Roosevelt Drive , Oxford OX3 7FZ , UK.,College of Food Science and Engineering, Ocean University of China, Qingdao, 266003, China.,Molecular Biophysics Unit, Indian Institute of Science, Bangalore, India. suguna@iisc.ac.in.,Physik Department E22, Technische Universität München, 85748 Garching, Germany.,From the Department of Biochemistry.,Children's Health Research Institute, Lawson Health Research Institute, 800 Commissioner's Road East, London, ON, N6C 2V5, Canada. sli@uwo.ca.,College of Pharmacy, Chung-Ang University, Seoul, 06974, Republic of Korea.,the Collaborative Research Institute for Innovative Microbiology, University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8657.,Schrödinger, GmbH, Q7 23, 681 61 Mannheim, Germany.,College of Food Science and Engineering, Ocean University of China, Qingdao, 266003, China. xzhmao@ouc.edu.cn.,The Francis Crick Institute , 1 Midland Road , London NW1 1AT , UK.,Department of Chemistry, Graduate School of Science, Chiba University, Chiba, Japan.,Howard Hughes Medical Institute, Harvard Medical School, Boston, MA 02115.,Department of Surgery, Ruhr-University Bochum, Knappschaftskrankenhaus, Bochum, Germany.,Laboratory of Biomolecular Research, Department of Biology and Chemistry, Paul Scherrer Institute, 5232 Villigen PSI, Switzerland; joerg.standfuss@psi.ch roger.dawson@roche.com.,State Key Laboratory of Membrane Biology, School of Life Sciences and School of Medicine, Tsinghua University, Beijing 100084, China. nyan@princeton.edu glenn.king@imb.uq.edu.au zhouq2015@mail.tsinghua.edu.cn.,Laboratorio Nacional de Genómica para la Biodiversidad, Centro de Investigación y de Estudios Avanzados del IPN, Guanajuato, Mexico.,Department of Neurobiology, Harvard Medical School, Boston, MA 02115.,Center for Biocrystallographic Research, Institute of Bioorganic Chemistry, Polish Academy of Sciences, Poznan, Poland.,Divisions of Vaccine Research and Clinical Care and Research, Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD 21201, USA; Department of Medicine, Baltimore VA Medical Center, Baltimore, MD 21201, USA; Department of Medicine, University of Maryland School of Medicine, Baltimore, MD 21201, USA. Electronic address: msajadi@ihv.umaryland.edu.,the Polymer Chemistry Group, Research Institute for Sustainable Chemistry, AIST, 1-1-1 Higashi, Tsukuba, Ibaraki 305-8565, Japan, and.,State Key Laboratory of Biotherapy, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, Chengdu 610041, China.,From the Department of Biotechnology and asfushi@mail.ecc.u-tokyo.ac.jp.,Faculty of Chemistry and Chemical Biology, TU Dortmund University, Dortmund, Germany.,the Department of Applied Biological Science, Faculty of Science and Technology, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 278-8510, Japan.,Department of Bacteriology, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan.,Department of Biochemistry & Structural Biology , Lund University , S-221 00 Lund , Sweden.,National Center for Protein Science Shanghai, Shanghai Institutes of Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.,Skaggs School of Pharmacy and Pharmaceutical Sciences , University of California, San Diego , La Jolla , California 92093 , United States.,School of Pharmaceutical Sciences, Beijing Advanced Innovation Center for Structural Biology, MOE Key Laboratory of Bioorganic Phosphorus Chemistry & Chemical Biology, Tsinghua University, Beijing 100084, China.,Department of Pharmaceutical Chemistry, University of California, San Francisco, CA 94158; liu_xy@mail.tsinghua.edu.cn bshoichet@gmail.com kobilka@stanford.edu peter.gmeiner@fau.de.,Institute of Biochemistry, Ernst-Moritz-Arndt University Greifswald, Felix-Hausdorff-Str. 4, 17487, Greifswald, Germany.,Department of Biochemistry, Vanderbilt University, Nashville, TN 37232-0146, USA.,Department of Physics, University of Oxford, Oxford OX1 3PU, UK.,Department of Medicine, University of Maryland School of Medicine, Baltimore, MD 21201, USA.,Dept. de Bioquímica i Biologia Molecular, Serra Hunter Fellow, Universitat Autònoma de Barcelona, Bellaterra, 08193, Spain.,Department of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, PA, 15260, USA.,School of Basic Medical Sciences, Nanchang University, Nanchang, 330031 Jiangxi, China.,The Rosalind Franklin Institute, Didcot, England.,German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), Heidelberg, Germany.,The Scripps Research Institute, La Jolla, 92037, USA. c.k.wibmer@gmail.com.,Department for Chemistry , University of Basel , BPR 1096, Mattenstrasse 24a , Basel , Switzerland.,Department of Molecular Biosciences, 1200 Sunnyside Ave, University of Kansas, Lawrence, KS, 66045, USA. Electronic address: lamb@ku.edu.,Department of Bioengineering, College of Life Science, Dalian Minzu University, Dalian, 116600, Liaoning, China.,Institute of Bioinformatics, University of Georgia, Athens, GA 30602, USA.,Division of Gastroenterology, Department of Internal Medicine, Graduate School of Medicine, Kobe University, Kobe, 650-0017, Japan.,Structural Molecular Biology, Stanford Synchroton Radiation Lightsource, SLAC National Accelerator Laboratory, Stanford University, Menlo Park, CA 94025.,Structural and Functional Biology Laboratory, National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi 110 067, India.,Griffith Institute for Drug Discovery, Griffith University, Nathan, QLD 4111, Australia.,Structural Genomics Consortium, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.,Hefei National Laboratory for Physical Science at Microscale and School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230026, People's Republic of China. Electronic address: tangyj@ustc.edu.cn.,Integrated Program in Neuroscience, McGill University, Montréal, QC H3A 2B4, Canada; Department of Pharmacology and Therapeutics, McGill University, Montréal, QC H3G 1Y6, Canada.,the Bio-based Materials Chemistry Group, Research Institute for Sustainable Chemistry, National Institute of Advanced Industrial Science and Technology (AIST), 3-11-32 Kagamiyama, Higashi-Hiroshima, Hiroshima 739-0046, Japan.,6Department of Pediatrics, and Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02215 USA.,Department of Biophysics, University of Texas Southwestern Medical Center, Dallas, TX, USA. Xuewu.Zhang@UTSouthwestern.edu.,Molecular and Cellular Biology PhD program, University of Washington, Seattle, Washington, United States of America.,Antibody Development and Protein Engineering, Gaithersburg, Maryland.,Department of Visceral and General Surgery, St. Josef Hospital, Ruhr-University Bochum, Germany.,Morgridge Institute for Research, Madison, WI, 53706, USA.,Michael Smith Laboratories, University of British Columbia, Vancouver, BC V6T 1Z4, Canada; Department of Biochemistry and Molecular Biology, University of British Columbia, Vancouver, BC V6T 1Z3, Canada. Electronic address: gsponer@msl.ubc.ca.,Independent consultant and collaborator with St. Jude Children's Research Hospital, Memphis, Tennessee, USA.,Department of Biosciences and Bioengineering, Indian Institute of Technology Bombay, Powai, Mumbai, 400 076, India.,School of Chemistry and Biochemistry , Georgia Institute of Technology , Atlanta , Georgia 30332 , United States.,Department of Integrative Structural and Computational Biology, Scripps Research Institute, La Jolla, CA, USA.,Department of Structural Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15260; acohen@slac.stanford.edu guc9@pitt.edu.,Department of Internal Medicine, St. Josefs-Hospital, Dortmund, Germany.,Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, CA, 94158, USA.,Department of Chemistry , The University of Texas at Austin , Austin , Texas 78712 , United States.,Department of Polar Sciences, University of Science and Technology, Incheon 21990, Republic of Korea.,Department of Pharmacology, University of Cambridge, Cambridge CB2 1PD, UK; Department of Physiology, Pontificia Universidad Católica de Chile, 8331150 Santiago, Chile.,Medicinal Chemistry, Monash Institute of Pharmaceutical Sciences , Monash University , Parkville Victoria 3052 , Australia.,National Key Laboratory of Plant Molecular Genetics, CAS Center for Excellence in Molecular Plant Sciences, Shanghai Center for Plant Stress Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, 201602, China. jmdu@sibs.ac.cn.,National Center for Global Health and Medicine Research Institute (NCGM), Tokyo, 162-8655, Japan; Experimental Retrovirology Section, HIV and AIDS Malignancy Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20892, USA; Department of Clinical Sciences, Kumamoto University Hospital, Kumamoto, 860-8556, Japan.,Department of Anesthesiology and Perioperative Medicine, University of Pittsburgh, Pittsburgh, PA, 15260, USA.,Krone Engineered Biosystems Building , Georgia Institute of Technology , Atlanta , Georgia 30332 , United States.,Department of Immunology, University of Toronto, Toronto, ON M5S 1A8, Canada.,Department of Biochemistry and Biophysics, Stockholm University, SE-106 91 Stockholm, Sweden.,Department of Pharmacology and Cancer Biology , Duke University School of Medicine , Durham , North Carolina 27710 , United States.,Department of Pharmacology and Therapeutics, McGill University, Montréal, QC H3G 1Y6, Canada. Electronic address: derek.bowie@mcgill.ca.,Department of Bioengineering, College of Life Science, Dalian Minzu University, Dalian, 116600, Liaoning, China; Key Laboratory of Biotechnology and Bioresources Utilization (Dalian Minzu University), Ministry of Education, China. Electronic address: yongbinxu@dlnu.edu.cn.,Division of Biology and Biological Engineering, California Institute of Technology, 1200 E. California Boulevard, Pasadena, CA 91125, USA.,Dept. de Bioquímica i Biologia Molecular, Serra Hunter Fellow, Universitat Autònoma de Barcelona, Bellaterra, 08193, Spain. david.reverter@uab.cat.,Department of Biochemistry, Howard Hughes Medical Institute, Brandeis University, Waltham, United States.,Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul, 08826, Republic of Korea.,the Department of Chemistry, University of Warwick, Warwick, Coventry CV4 7AL, United Kingdom.,Experimental Center, Technische Universität Dresden, Faculty of Medicine, Fiedlerstraße 42, 01307 Dresden, Germany.,Center for Precision Medicine Multi-Omics Research, Peking University Health Science Center, Beijing 100191, China.,Department of Molecular and Cellular Biochemistry , Indiana University , Bloomington , Indiana 47405 United States.,Sorbonne Université, Institut Curie, CNRS, UMR3664, F-75005, Paris, France.,Department of Microbiology, Biochemistry and Molecular Genetics, Center for Immunity and Inflammation, Rutgers Cancer Institute of New Jersey at University Hospital, New Jersey Medical School, Rutgers University, Newark, NJ 07103; and.,Division of Experimental Medicine, Beth Israel Deaconess Medical Center, Boston, MA 02215.,Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003, Lisbon, Portugal.,From the Molecular Biology and.,Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720, USA.,University of Florence , NEUROFARBA Dept., Sezione di Scienze Farmaceutiche , Via Ugo Schiff 6 , 50019 Sesto Fiorentino ( Florence ), Italy.,Oncology Group, Northern Biologics, Toronto, ON M5G 1L7, Canada; jfransson@northernbiologics.com jean-philippe.julien@sickkids.ca.,Department of Pharmaceutical Sciences, University of Connecticut , 69 North Eagleville Road, Storrs, Connecticut 06269, United States.,Department of Agricultural Biotechnology, College of Agriculture and Life Sciences, Seoul National University, Gwanak-gu, Seoul, 08826, Republic of Korea.,Department of Microbiology, Immunology and Infectious Diseases, University of Calgary, 2500 University Dr. NW, Calgary, AB, T2N 1N4, Canada.,c Collaborative Innovation Center of Chemistry for Life Sciences , Shanghai Institute of Organic Chemistry, University of Chinese Academy of Sciences, Chinese Academy of Sciences , Shanghai , China.,Department of Pharmaceutical Sciences, Albany College of Pharmacy and Health Sciences, Colchester, Vermont.,Department of Chemistry and Chemical Biology , Cornell University , Ithaca , New York 14853 , United States.,Department of Pharmacology and Physiology , Saint Louis University School of Medicine , M370, Schwitalla Hall, 1402 South Grand Boulevard , Saint Louis , Missouri 63104 , United States.,1College of Life Science and Technology, Huazhong Agricultural University, Wuhan, 430070 China.,Department of Bionanoengineering, Hanyang University, Kyunggi-do 15588, Republic of Korea.,Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003, Lisbon, Portugal. sdlucas@ff.ulisboa.pt.,Laboratory of Genetics, University of Wisconsin-Madison, Madison, WI, 53706, USA. xuehua.zhong@wisc.edu.,Genome Integrity and Structural Biology Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, 111T. W. Alexander Drive, Research Triangle Park, NC, 27709, USA.,CNRS CEA Université Paris Sud, Université Paris-Saclay, Institute for Integrative Biology of the Cell (I2BC), Avenue de la Terrasse, 91198 Gif-sur-Yvette, France.,Center for Matrix Biology, Vanderbilt University Medical Center, Nashville, TN 37232, USA.,Pharmaceutical Sciences, University of Tennessee Health Science Center, Memphis, TN, United States.,Department of Chemistry and Biochemistry , Miami University , 651 East High Street, 160 Hughes Laboratories , Oxford , Ohio 45056 , United States.,Department of Chemical Biology & Therapeutics, St. Jude Children's Research Hospital, Memphis, TN, United States.,Department of Microbiology and Immunology, Montana State University, Bozeman, MT 59717, USA.,School of Life Sciences, KNU Creative BioResearch Group, Kyungpook National University, Daegu 41566, Republic of Koreaa.,From the Institute of Biological Chemistry and Core Facilities for Protein Structural Analysis, Academia Sinica, Taipei 11529 and.,Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115.,Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, 240 Longwood Avenue, Boston, MA, 02115, USA.,Finsen Laboratory, Rigshospitalet, DK-2200 Copenhagen, Denmark.,Michael Smith Laboratories, University of British Columbia, Vancouver, BC V6T 1Z4, Canada; Department of Biochemistry and Molecular Biology, University of British Columbia, Vancouver, BC V6T 1Z3, Canada; Department of Chemistry, University of British Columbia, Vancouver, BC V6T 1Z1, Canada. Electronic address: mcintosh@chem.ubc.ca.,Department of Pathology, University of Cambridge, Cambridge CB2 1QP, United Kingdom vk103@cam.ac.uk.,Departamento de Microbiología, Facultad de Medicina at Universitat de València, Blasco Ibáñez 17, 46010 Valencia, Spain.,Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul, 08826, Republic of Korea. bwhan@snu.ac.kr.,Lead Discovery Center GmbH, Dortmund, Germany.,Division of Structural Biology, Wellcome Trust Centre of Human Genomics, Oxford, England.,Infectious Diseases, St. Jude Children's Research Hospital, Memphis, TN, United States.,Department of Biochemistry, University of Cambridge, Cambridge, UK lp212@cam.ac.uk g.j.l.wuite@vu.nl e.j.g.peterman@vu.nl.,Hefei National Laboratory for Physical Science at Microscale and School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230026, People's Republic of China. Electronic address: yyshi@ustc.edu.cn.,Janelia Farm Research Campus, Howard Hughes Medical Institute, Ashburn, VA 20147.,Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX, USA.,Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, TX, USA. Xuewu.Zhang@UTSouthwestern.edu.,Department of Biochemistry, Schulich School of Medicine and Dentistry, Western University, London, ON, N6A 5C1, Canada. sli@uwo.ca.,From the School of Life Sciences and.,Department of Chemistry and Pharmacy, Medicinal Chemistry, Friedrich-Alexander-Universität Erlangen-Nürnberg, 91058 Erlangen, Germany.,Instituto de Biomedicina de Valencia, Consejo Superior de Investigaciones Científicas (IBV-CSIC), Jaume Roig 11, 46010 Valencia, Spain.,Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA 91125.,National Center for Global Health and Medicine Research Institute (NCGM), Tokyo, 162-8655, Japan.,Roche Pharma Research and Early Development, Therapeutic Modalities, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd, 4070 Basel, Switzerland; joerg.standfuss@psi.ch roger.dawson@roche.com.,Gene Center Munich and Center of Integrated Protein Science-Munich (CiPS-M), Department of Biochemistry, University of Munich, Munich, Germany. beckmann@genzentrum.lmu.de.,Department of Biomaterial Sciences, Graduate School of Agricultural and Life Sciences, University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8657, Japan.,Schrödinger, Inc., 120 West 45(th) Street, New York, NY 10036, USA.,Department of Microbiology and Molecular Genetics, University of Vermont, Burlington, Vermont.,Department of Chemistry, The University of Western Ontario, London, ON, Canada.,Department of Neurology, Chonbuk National University School of Medicine, Jeonju 54896, Republic of Korea.,Institut de Biotecnologia i de Biomedicina (IBB), Universitat Autònoma de Barcelona, Bellaterra, 08193, Spain. david.reverter@uab.cat.,From the Shanghai Institute of Applied Physics, Chinese Academy of Sciences, Shanghai 201800 and.,Program in Molecular Medicine, Hospital for Sick Children Research Institute, Toronto, ON M5G 0A4, Canada; jfransson@northernbiologics.com jean-philippe.julien@sickkids.ca.,Structural Molecular Biology, Stanford Synchroton Radiation Lightsource, SLAC National Accelerator Laboratory, Stanford University, Menlo Park, CA 94025; acohen@slac.stanford.edu guc9@pitt.edu.,Chemistry Research Laboratory , Department of Chemistry , University of Oxford , Oxford OX1 3TA , UK . Email: christopher.schofield@chem.ox.ac.uk.,Midwest Center for Structural Genomics and Structural Biology Center, Biosciences, Argonne National Laboratory, Lemont, Illinois, USA.,Genome Science and Technology Program, University of British Columbia, Vancouver, BC V6T 1Z4, Canada; Michael Smith Laboratories, University of British Columbia, Vancouver, BC V6T 1Z4, Canada.,Division of Biology and Biological Engineering, California Institute of Technology, 1200 E. California Boulevard, Pasadena, CA 91125, USA. Electronic address: bjorkman@caltech.edu.,Department of Environmental Microbiology, Institute of Water and Wetland Research, Radboud University, Nijmegen, The Netherlands.,Department of Computer Science and Engineering , Texas A&M University , 3112 TAMU , College Station , Texas 77842 , United States.,Department of Biological Science, Graduate School of Science, Osaka Prefecture University, 1-1 Gakuen-cho, Naka-ku, Sakai, Osaka 599-8531, Japan.,State Key Laboratory of Molecular Biology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai 200031, China.,Department of Drug Design and Pharmacology, University of Copenhagen, 2100 Copenhagen, Denmark.,Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.,Shandong Provincial Key Laboratory of Synthetic Biology and CAS Key Laboratory of Biofuels, Qingdao Institute of Bioenergy and Bioprocess Technology, Chinese Academy of Sciences, Songling Road 189, Qingdao, Shandong 266101, China. cuiqiu@qibebt.ac.cn fengyg@qibebt.ac.cn.,Departments of Medicine, Pharmacology, Molecular Biology and Microbiology, Biochemistry, Proteomics, and Bioinformatics and CWRU-Cleveland VAMC Center for Antimicrobial Resistance and Epidemiology , Case Western Reserve University , Cleveland , Ohio 44106 , United States.,Neutron Scattering Division , Oak Ridge National Laboratory , 1 Bethel Valley Road , Oak Ridge , Tennessee 37831 , United States.,Division of Innate Immunity, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.,Biochemistry Department, School of Biomedical Sciences, University of Otago, P.O. Box 56, 710 Cumberland Street, Dunedin 9054, New Zealand.,Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA 90095; sgyoung@mednet.ucla.edu mmeiyappan@shire.com.,Environmental Safety Center, Kumamoto University, Kumamoto, Japan.,Center for Disease Control and Prevention of Chinese PLA, Beijing, 100071, China; Academy of Military Medical Sciences, 27(#) Taiping Road, Haidian District, Beijing, 100101, China; Comprehensive Liver Cancer Center, 302 Military Hospital, Beijing, China.,Cell Adhesion Laboratory, Department of Integrative Structural and Computational Biology, The Scripps Research Institute, Jupiter, FL 33458.,Department of Cardiology, Boston Children's Hospital, Boston, MA 02115.,Division of Chemical Biology and Medicinal Chemistry, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.,Department of Physiology, School of Basic Medicine and Tongji Medical College, Huazhong University of Science and Technology, Wuhan 4030030, China; The Institute for Brain Research, Collaborative Innovation Center for Brain Science, Huazhong University of Science and Technology, Wuhan 430030, China.,Centre for HIV and STIs, National Institute for Communicable Diseases (NICD), of the National Health Laboratory Service (NHLS), Johannesburg, 2131, South Africa. c.k.wibmer@gmail.com.,Department of Defense, Center for Prostate Disease Research, Bethesda, Maryland, USA.,Centro de Investigaciones Biológicas (CSIC), Ramiro de Maeztu 9, 28040 Madrid, Spain.,Chan Zuckerberg Biohub, San Francisco, CA, 94158, USA.,INRA, USC 1408 AFMB, Marseille, France.,Department of Chemistry and Institute for Molecular Biology and Genetics, Chonbuk National University, Jeonju 54896, Republic of Korea.,Cecil H. and Ida Green Center for Reproductive Biology Sciences and Division of Basic Research, Department of Obstetrics and Gynecology, Department of Biophysics, UT Southwestern Medical Center, Dallas, TX, 75390, USA.,Department of Structural Biology, University of Pittsburgh, Pittsburgh, PA, 15260, USA.,Department of Biochemistry, The University of Western Ontario, London, ON, Canada gshaw1@uwo.ca.,Department of Chemistry and Biochemistry, 3210 N Cramer St, University of Wisconsin-Milwaukee, Milwaukee, WI, 53211, USA.,Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Department, Department of Chemistry, School of Chemistry and Molecular Engineering, East China Normal University, Shanghai, 200062, China.,Division of Molecular Cell Biology, Core Research Facilities for Basic Science, Research Center for Medical Sciences, The Jikei University School of Medicine, Chiba, Japan.,CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China; Savaid Medical School, University of Chinese Academy of Sciences, Beijing 100049, China. Electronic address: jxqi@im.ac.cn.,School of Biological Sciences , Georgia Institute of Technology , Atlanta , Georgia 30332 , United States.,Signal Transduction Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, 111T. W. Alexander Drive, Research Triangle Park, NC, 27709, USA.,Department of Chemistry , Indiana University , Bloomington , Indiana 47405-7102 United States.,Department of Visceral and General Surgery, St. Josefs-Hospital, Dortmund, Germany.,Department of Pharmacology, Yale University School of Medicine, New Haven, CT 06520, USA; Cancer Biology Institute, Yale University, West Haven, CT 06516, USA.,Department of Microbiology and Immunology, Montana State University, Bozeman, MT 59717, USA. Electronic address: bwiedenheft@gmail.com.,Bioproduction Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), Sapporo, 062-8517, Japan; Computational Bio Big-Data Open Innovation Laboratory (CBBD-OIL), AIST, Sapporo, 062-8517, Japan. Electronic address: y-yasutake@aist.go.jp.,Structural Genomics Consortium (SGC) , University of Oxford , Oxford OX3 7DQ , UK.,the Department of Biochemical Science and Technology, College of Life Science, Institute of Biotechnology, College of Bio-Resources and Agriculture, National Taiwan University, Taipei 10617, Taiwan chiishen@ntu.edu.tw.,Cancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing Centre, Cambridge CB2 0RE, UK.,Department of Anesthesiology and Perioperative Medicine, University of Pittsburgh, Pittsburgh, PA, 15260, USA. ptang@pitt.edu.,Department of Organic Chemistry, University of Debrecen, POB 400, H-4002 Debrecen, Hungary. Electronic address: somsak@tigris.unideb.hu.,Key Laboratory of Drug Targeting and Drug Delivery System of Ministry of Education, West China School of Pharmacy, and State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu, 610041, China; College of Food and Bioengineering, Xihua University, Sichuan, 610039, China.,Nimbus Therapeutics, Cambridge, MA, USA.,Macromolecular Crystallography Laboratory, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702.,Cancer Research Center of Marseille, CNRS UMR7258, Inserm U1068, Institut Paoli-Calmettes, Aix-Marseille Université, Marseille, France.,3State Key Laboratory of Membrane Biology, College of Life Sciences, Peking University, Beijing, 100871 China.,Australian Synchrotron , Victoria 3168 , Australia.,Department of Agricultural Biotechnology, Seoul National University, 1 Gwanak-ro, Seoul 08826, Republic of Korea.,Microbial Sciences, Gaithersburg, Maryland.,Protein Structure Section, Macromolecular Crystallography Laboratory, National Cancer Institute, Frederick, MD 21702, USA.,X-ray Science Division, Advanced Photon Source, Argonne National Laboratory, Argonne, IL 60349, USA.,Architecture et Fonction des Macromolécules Biologiques, Centre National de la Recherche Scientifique (CNRS), Aix-Marseille University, Marseille, France.,Department of Chemistry , King's College London , 7 Trinity Street , London SE1 1DB , U.K.,Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA, 02215, USA.,Department of Chemistry and Biochemistry, 1068 W Sheridan Rd, Loyola University Chicago, Chicago, IL, 60660, USA.,Department of Chemistry and Biochemistry, University of California, Los Angeles, CA 90095.,Laboratorio de Investigación Bioquímica, Programa Institucional en Biomedicina Molecular ENMyH-IPN, Ciudad de México, Mexico.,From the School of Life Sciences and e.fullam@warwick.ac.uk.,Department of Chemistry , Tokyo Institute of Technology , 2-12-1 O-okayama , Meguro-ku, Tokyo 152-8551 , Japan.,State Key Laboratory of Bio-organic and Natural Products Chemistry, Chinese Academy of Sciences, Shanghai Institute of Organic Chemistry, Shanghai, 200032, China.,the Graduate School of Advanced Sciences of Matter, Hiroshima University, 1-3-1 Kagamiyama, Higashi-Hiroshima, Hiroshima 739-8530, Japan.,Biomedical Sciences Research Complex, The University of St Andrews, Scotland, United Kingdom.,Pharmaron Beijing Co., Ltd. , No. 6 Taihe Road, BDA , Beijing 100176 , P. R. China.,Molecular Chirality Research Center, Chiba University, Chiba, Japan.,Graduate Program in Biophysics, Harvard University, Cambridge, MA, 02138, USA.,Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, 20892, USA.,Department of Chemistry, University of California Berkeley, Berkeley, CA, 94720, USA.,Unit of Polar Genomics, Korea Polar Research Institute, Incheon 21990, Republic of Korea.,Signal Transduction Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, 111T. W. Alexander Drive, Research Triangle Park, NC, 27709, USA. robin.stanley@nih.gov.,Bioprospecting Group, Agharkar Research Institute, Pune, 411 004, India.,School of Pharmaceutical Sciences, Beijing Advanced Innovation Center for Structural Biology, MOE Key Laboratory of Bioorganic Phosphorus Chemistry & Chemical Biology, Tsinghua University, Beijing 100084, China; Joint Graduate Program of Peking-Tsinghua-NIBS, School of Life Sciences, Tsinghua University, Beijing 100084, China.,Institut Laue-Langevin , 71 avenue des Martyrs , 38000 Grenoble , France.,Structural Biology Unit, Institut de Biología Molecular de Barcelona CSIC, Barcelona, Spain.,Institute of Human Virology, School of Medicine, University of Maryland, 725 W Lombard St, Baltimore, MD, 21201, USA.,MRC Protein Phosphorylation and Ubiquitylation Unit, School of Life Sciences, University of Dundee, Dundee DD1 5EH, UK pawel.leznicki@manchester.ac.uk ykulathu@dundee.ac.uk.,Department of Biomolecular Engineering, University of California, Santa Cruz, Santa Cruz, CA 95064.,Department of Bioscience, Tokyo University of Agriculture, Sakuragaoka 1-1-1, Setagaya, Tokyo, 156-8502, Japan.,Department of Biology, ETH Zurich, 8093 Zurich, Switzerland.,National Center for Protein Science Shanghai, Shanghai Institutes of Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China; National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.,CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China; Savaid Medical School, University of Chinese Academy of Sciences, Beijing 100049, China. Electronic address: wenty@im.ac.cn.,Department of Biology, 1205 Avenue Docteur Penfield, Montréal, QC H3A 1B1, Canada.,Department of Chemistry, Durham University, Science Laboratories, South Road, Durham, DH1 3LE, U.K.,Evergrande Center for Immunologic Diseases and Ann Romney Center for Neurologic Diseases, Harvard Medical School and Brigham and Women's Hospital, 77 Avenue Louis Pasteur, Boston, MA, 02115, USA.,Leibniz Research Centre for Working Environment and Human Factors (IfADo), TU Dortmund University, Dortmund, Germany.,Divisions of Vaccine Research and Clinical Care and Research, Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD 21201, USA.,RIKEN Center for Biosystems Dynamics Research, Suehiro-cho, Tsurumi-ku, Yokohama 230-0045, Japan. takuhiro.ito@riken.jp.,Department of Biomolecular Chemistry, University of Wisconsin-Madison, Madison, WI, 53706, USA.,Vanderbilt Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA.,School of Food Science and Engineering, South China University of Technology, Guangzhou, PR China.,Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.,Department of Biological Sciences, Columbia University, New York, NY, USA. ltong@columbia.edu.,b Interdisciplinary Research Center on Biology and Chemistry , Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences , Shanghai , China.,Department of Integrative Oncology , BC Cancer Research Centre , V5Z 1L3 Vancouver Vancouver , British Columbia , Canada.,Gene Center, Ludwig-Maximilians-University, 81377 Munich, Germany.,Structural Biology Research Center (SBRC), Institute of Materials Structure Science (IMSS), High Energy Accelerator Research Organization (KEK), 1-1 Oho, Tsukuba, Ibaraki, 305-0801, Japan.,Institut Curie, PSL Research University, CNRS, UMR3664, Equipe Labellisée Ligue contre le Cancer, F-75005, Paris, France. almouzni@curie.fr.,Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, UK.,Hefei National Laboratory for Physical Sciences at Microscale and School of Life Sciences, Collaborative Innovation Center of Chemistry for Life Science, University of Science and Technology of China, 96 Jinzhai Road, Hefei, Anhui 230026, People's Republic of China.,Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, Tennessee, USA elena.govorkova@stjude.org.,Institute for Molecular Bioscience, The University of Queensland, St. Lucia, Queensland 4072, Australia. nyan@princeton.edu glenn.king@imb.uq.edu.au zhouq2015@mail.tsinghua.edu.cn.,CNRS CEA Université Paris Sud, Université Paris-Saclay, Institute for Integrative Biology of the Cell (I2BC), Avenue de la Terrasse, 91198 Gif-sur-Yvette, France solange.morera@i2bc.paris-saclay.fr.,Swanson School of Engineering, University of Pittsburgh, Pittsburgh, PA 15260.,From the Shanghai Institute of Applied Physics, Chinese Academy of Sciences, Shanghai 201800 and yufeng@sinap.ac.cn.,The National Resource for Automated Molecular Microscopy, Simons Electron Microscopy Center, New York Structural Biology Center, New York NY 10027, USA.,Department of Molecular Biosciences, 1200 Sunnyside Ave, University of Kansas, Lawrence, KS, 66045, USA.,Department of Biochemistry and Molecular Biology, School of Medicine , Oregon Health & Science University , Portland , Oregon 97239 , United States.,College of Medicine, Seoul National University, Seoul, 03080, Republic of Korea. swkimmd@snu.ac.kr.,Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Parkville, Australia. mhinds@unimelb.edu.au.,From the Bioconversion Group and.,Translational Medicine, Gaithersburg, Maryland.,Department of Chemistry, University of Cambridge, Cambridge CB2 1EW, UK.,Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Melbourne, Victoria, 3086, Australia. m.kvansakul@latrobe.edu.au.,Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, CA, 94158, USA. jfraser@fraserlab.com.,Bioproduction Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), Sapporo, 062-8517, Japan.,Department of Life Sciences, Imperial College, London, SW7 2AZ, UK.,Department of Cardiology, Boston Children's Hospital, Boston, MA 02115; zhangxiaokong@hotmail.com claphamd@hhmi.org.,Department of Biochemistry and Molecular Cell Biology, State Key Laboratory of Oncogenes and Related Genes, Shanghai Key Laboratory of Tumor Microenvironment and Inflammation, Shanghai Jiao-Tong University School of Medicine, Shanghai, China.,Waksman Institute and Department of Chemistry, Rutgers University, Piscataway, NJ 08854, USA.,Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, TX, USA. Zhijian.Chen@UTSouthwestern.edu.,Inositol Signaling Group, Signal Transduction Laboratory , National Institute of Environmental Health Sciences , Research Triangle Park , North Carolina 27709 , United States.,Max-Planck-Institut für Kohlenforschung , Kaiser-Wilhelm-Platz 1, 45470 Mülheim an der Ruhr, Germany.,Institut de Investigacions Biomèdiques Agustí Pi i Sunyer (IDIBABS), Barcelona, 08036, Spain.,Department of Biophysics, University of Texas Southwestern Medical Center, Dallas, TX, USA. Xiaochen.Bai@UTSouthwestern.edu.,Global Medicines Development, AstraZeneca, Waltham, Massachusetts.,Beijing Advanced Innovation Center for Structural Biology, School of Medicine, Tsinghua University, 100084 Beijing, China; liu_xy@mail.tsinghua.edu.cn bshoichet@gmail.com kobilka@stanford.edu peter.gmeiner@fau.de.,College of Pharmacy, Kinjo Gakuin University, Nagoya, Aichi, Japan.,Julius-Maximilians-Universität Würzburg, Josef Schneider Straße 2, 97080 Würzburg, Germany.,Biostatistics, MedImmune, Gaithersburg, Maryland.,Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USA.,Center for Disease Control and Prevention of Chinese PLA, Beijing, 100071, China. Electronic address: hanlicdc@163.com.,Institute of Immunology, Tsinghua University, Beijing 100084, China.,Institute for Genomic Biology, and.,Graduate School of Pharmaceutical Sciences, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo 113-0033, Japan. Electronic address: shimizu@mol.f.u-tokyo.ac.jp.,Agricultural Bioinformatics Research Unit, and.,Department of Biochemistry, The University of Western Ontario, London, ON, Canada.,Beijing Advanced Innovation Center for Structural Biology, Tsinghua-Peking Joint Center for Life Sciences, School of Life Sciences and School of Medicine, Tsinghua University, Beijing 100084, China.,The Henry Wellcome Building for Biocatalysis, Biosciences, College of Life and Environmental Sciences, University of Exeter, Exeter, United Kingdom.,Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.,Division of Life Science, State Key Laboratory of Molecular Neuroscience, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China.,Department of Chemistry, University of Pittsburgh, 219 Parkman Avenue, Pittsburgh, PA, 15260, USA.,BioStratum Inc., Durham, North Carolina, USA.,the VTT Technical Research Centre of Finland, Espoo FI-02044 VTT, Finland, and.,State Key Laboratory of Membrane Biology, School of Life Sciences and School of Medicine, Tsinghua University, Beijing 100084, China.,Dipartimento di Scienze degli Alimenti e del Farmaco , Università di Parma , 43124 Parma , Italy.,College of Food and Bioengineering, Xihua University, Sichuan, 610039, China.,2Department of Medical Oncology, and Cancer Biology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215 USA.,Laboratory of Molecular Modeling and Design, State Key Laboratory of Molecular Reaction Dynamics, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, China.,Department of Biomedical Engineering, 2200 Bonisteel Boulevard, Ann Arbor, MI 48109, USA.,Department of Chemical Engineering and Applied Chemistry, University of Toronto, Toronto, ON, M5G 1L6, Canada.,National Key Laboratory of Plant Molecular Genetics, CAS Center for Excellence in Molecular Plant Sciences, Shanghai Center for Plant Stress Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, 201602, China.,a State Key Laboratory of Bioorganic and Natural Products Chemistry , Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences , Shanghai , China.,Department of Chemistry, Grand Valley State University , Allendale, Michigan 49401, United States.,Department of Biochemistry, University of Zurich, Zurich, Switzerland.,Department of Biophysical Chemistry , Lund University , S-221 00 Lund , Sweden.,Discovery Therapeutics, US Drug Discovery, Shire Pharmaceuticals, Cambridge, MA 02142; sgyoung@mednet.ucla.edu mmeiyappan@shire.com.,Department of Chemistry , Texas A&M University , College Station , Texas 77843 , United States.,Department of Chemistry - BMC, Uppsala University, Box 576, SE-75123 Uppsala, Sweden dobritzsch@kemi.uu.se.,Department of Life Science, Faculty of Advanced Engineering, Chiba Institute of Technology, Chiba, Japan.,Howard Hughes Medical Institute and Department of Biochemistry, Brandeis University, 415 South Street, Waltham, MA, 02454, USA.,Department of Computational and Systems Biology, University of Pittsburgh, Pittsburgh, PA, 15260, USA. ptang@pitt.edu.,University of Florence , Department of Chemistry "Ugo Schiff" , Via della Lastruccia 3 , 50019 Sesto Fiorentino ( Florence ), Italy.,Department of Biochemistry, Schulich School of Medicine and Dentistry, Western University, London, ON, N6A 5C1, Canada.,Biozentrum, University of Basel, 4056 Basel, Switzerland.,Center for Interdisciplinary Biosciences, Technology and Innovation Park, P.J. Šafárik University, 041 54 Košice, Slovakia.,Department of Biochemistry and Biophysics, Karolinska Institutet, SE-17177 Stockholm, Sweden.,Sorbonne Université, Institut Curie, CNRS, UMR3664, F-75005, Paris, France. almouzni@curie.fr.,Department of Cell and Developmental Biology, Vanderbilt University Medical Center, Nashville, TN 37232, USA.,Anhui Province Key Laboratory of Medical Physics and Technology, Center of Medical Physics and Technology, Chinese Academy of Sciences, Hefei, Anhui, People's Republic of China.,Department of Pathophysiology, Key Laboratory of Cell Differentiation and Apoptosis of Ministry of Education, Shanghai Jiao-Tong University School of Medicine, Shanghai, China.,Microbial Protein Structure Group, Max Planck Institute for Terrestrial Microbiology, Karl-von-Frisch-Str. 10, 35043, Marburg, Germany.,Department of Pathology, University of Cambridge, Cambridge CB2 1QP, United Kingdom.,Macromolecular Crystallography Laboratory, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702; lubkowsj@mail.nih.gov.,Department of Neurology and Feil Family Brain and Mind Research Institute, Weill Cornell Medical College, New York, NY, 10021, USA.,Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai, China.,State Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai 200031, China.,From the Departments of Medicinal Chemistry and.,Key Laboratory of Drug Targeting and Drug Delivery System of Ministry of Education, West China School of Pharmacy, and State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu, 610041, China.,Tsinghua-Peking Joint Center for Life Sciences, School of Life Sciences and School of Medicine, Tsinghua University, Beijing 100084, China.,Department of Metallurgical Engineering and Materials Science, Indian Institute of Technology Bombay, Powai, Mumbai, 400 076, India.,Department of Molecular Physiology and Biological Physics, University of Virginia, Charlottesville, VA 22908, USA; Center for Structural Genomics of Infectious Diseases, Charlottesville, VA 22908, USA.,Oncology Group, Northern Biologics, Toronto, ON M5G 1L7, Canada.,Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 1A8, Canada.,Department of Biochemistry, McGill University, Montreal, Quebec, Canada.,Institute of Health Sciences, Shanghai Institutes for Biological Sciences of Chinese Academy of Sciences and Shanghai Jiao-Tong University School of Medicine, Shanghai, China.,the Department of Biochemical Science and Technology, College of Life Science, Yen Tjing Ling Industrial Research Institute, and.,UCB/Beryllium Discovery, 98110, 7869 NE Day Road West, Bainbridge Island, WA, USA.,Institut de Biotecnologia i de Biomedicina (IBB), Universitat Autònoma de Barcelona, Bellaterra, 08193, Spain.,Department of Chemistry, UiT The Arctic University of Norway, N-9037 Tromsø, Norway.,Pharmacology and the Program in Biophysics, University of Michigan, Ann Arbor, Michigan 48109.,Laboratorio de Estructura Biomolecular, Centro de Investigación en Alimentación y Desarrollo, A.C., Hermosillo, Mexico.,Department of Biochemistry and Biophysics , Texas A&M University , 3112 TAMU , College Station , Texas 77842 , United States.,MRC Protein Phosphorylation and Ubiquitylation Unit, School of Life Sciences, University of Dundee, Dundee DD1 5EH, UK.,Department of Chemistry, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA. Electronic address: eoldfiel@illinois.edu.,Medical Research Institute, Tokyo Medical and Dental University (TMDU), 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510, Japan.,Department of Medicine, School of Medicine, University of Maryland, Baltimore, MD, 21201, USA.,Center for Disease Control and Prevention of Chinese PLA, Beijing, 100071, China; Academy of Military Medical Sciences, 27(#) Taiping Road, Haidian District, Beijing, 100101, China; Key Laboratory of Optoelectronic Devices and Systems of Ministry of Education and Guangdong Province, College of Optoelectronic Engineering, Shenzhen University, Shenzhen, China.,Department of Microbiology and Immunology, School of Medicine, University of Maryland, Baltimore, MD, 21201, USA.,College of Pharmacy, Pusan National University, Busandaehak-ro, Pusan 46241, Republic of Korea.,From the UMR Ecologie Microbienne, CNRS, INRA, VetAgro Sup, UCBL, Université de Lyon, F-69622, Villeurbanne, Lyon, France and.,Department of Computational Medicine and Bioinformatics, 100 Washtenaw Avenue, Ann Arbor, MI 48109, USA.,Department of Internal Medicine, Ruhr-University Bochum, Knappschaftskrankenhaus, Bochum, Germany.,State Key Laboratory of High Performance Ceramics and Superfine Microstructure, Shanghai Institute of Ceramics, Chinese Academy of Sciences, Shanghai, China.,State Key Laboratory of Bio-organic and Natural Products Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences , Shanghai 200032, China.,Center for Oceans and Human Health, Scripps Institution of Oceanography , University of California, San Diego , La Jolla , California 92093 , United States.,Department of Anatomy and Cell Biology, 3640 Rue University, Montréal, QC H3A 0C7, Canada.,CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.,Division of Infectious Diseases, Department of Medicine, University of British Columbia, Vancouver, BC V6H 3Z6, Canada; Department of Microbiology and Immunology, University of British Columbia, Vancouver, BC V6T 1Z3, Canada.,Laboratorio de Reconocimiento Molecular, Centro de Investigación Príncipe Felipe, Eduardo Primo Yúfera 3, 46012 Valencia, Spain.,Institute for Molecular Bioscience, The University of Queensland, St Lucia, QLD 4072, Australia.,Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, 2000, South Africa. c.k.wibmer@gmail.com.,Department of Pharmacology and Therapeutics, McGill University, Montréal, QC H3G 1Y6, Canada.,From the Department of Biotechnology.,Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Krakow, Poland; Malopolska Centre of Biotechnology, Jagiellonian University, Krakow, Poland.,Structure and Function of Proteins , Helmholtz Centre for Infection Research , Inhoffenstr. 7 , 38124 , Braunschweig , Germany.,Departamento de Bioquímica y Biología Molecular at Facultad de Medicina y Odontología, Universitat de València, Blasco Ibáñez 15-17, 46010 Valencia, Spain.,Technology Center for Protein Sciences, Ministry of Education Key Laboratory of Protein Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China.,Heinz Maier-Leibnitz Zentrum (MLZ) , Technische Universität München , Lichtenbergstrasse 1 , 85748 Garching , Germany.,Center for Integrative Proteomics, Rutgers University, Piscataway, NJ 08854, USA.,Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, 2000, South Africa.,Howard Hughes Medical Institute and Department of Biochemistry, Brandeis University, 415 South Street, Waltham, MA, 02454, USA. dkern@brandeis.edu.,Department of Biochemistry and Biophysics, Graduate Group in Biochemistry and Molecular Biophysics, Abramson Family Cancer Research Institute, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, 19104, USA.,Department of Environmental Microbiology, Institute of Water and Wetland Research, Radboud University, Nijmegen, The Netherlands ktan@anl.gov c.welte@science.ru.nl.,Center for Disease Control and Prevention of Chinese PLA, Beijing, 100071, China; Academy of Military Medical Sciences, 27(#) Taiping Road, Haidian District, Beijing, 100101, China.,Novozymes A/S, Krogshoejvej 36, 2880, Bagsvaerd, Denmark.,Department of Microbiology, Faculty of Biotechnology and Biomolecular Sciences , Universiti Putra , 43400 Seri Kembangan , Selangor , Malaysia.,National Center for Global Health and Medicine Research Institute (NCGM), Tokyo, 162-8655, Japan. Electronic address: kmaeda@ri.ncgm.go.jp.,Cell Adhesion Laboratory, Department of Integrative Structural and Computational Biology, The Scripps Research Institute, Jupiter, FL 33458 cmorrow@scripps.edu.,Center for Computational Quantum Chemistry, Department of Chemistry , University of Georgia , 140 Cedar Street , Athens , Georgia 30602-2556 , United States.,Research Service , Louis Stokes Cleveland Department of Veterans Affairs Medical Center , Cleveland , Ohio 44106 , United States.,Department of Structural Biology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.,School of Pharmaceutical Sciences, Beijing Advanced Innovation Center for Structural Biology, MOE Key Laboratory of Bioorganic Phosphorus Chemistry & Chemical Biology, Tsinghua University, Beijing 100084, China. Electronic address: zhangyonghui@tsinghua.edu.cn.,Department of Physics, University of Cagliari, Cagliari, Italy.,Basic Sciences Division and Computational Biology Program, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.,Michael Smith Laboratories, University of British Columbia, Vancouver, BC V6T 1Z4, Canada.,Beijing Advanced Innovation Center for Structural Biology, School of Life Sciences and School of Medicine, Tsinghua University, Beijing 100084, China.,d Department of Cell Biology , Harvard Medical School , Boston , MA , USA.,Center for Biocrystallographic Research, Institute of Bioorganic Chemistry, Polish Academy of Sciences, Poznan, Poland; Department of Crystallography, Faculty of Chemistry, A. Mickiewicz University, Poznan, Poland. Electronic address: mariuszj@amu.edu.pl.,Center for Biophysics and Computational Biology, University of Illinois at Urbana Champaign, Urbana, Illinois 61801 and.,CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China.,Grupo Interdisciplinar de Sistemas Complejos (GISC) and Departamento de Matemáticas, Universidad Carlos III de Madrid, 28911 Leganes, Spain.,Key Laboratory of Drug Targeting and Drug Delivery System of Ministry of Education, West China School of Pharmacy, and State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu, 610041, China. Electronic address: qiang_chen@scu.edu.cn.,Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, CA 94305.,Centre for the Analysis of Genome Evolution and Function, University of Toronto, Toronto, ON, M5S 3B2, Canada.,Department of Biochemistry and Biophysics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, 19104, USA.,Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, UK. Electronic address: spring@ch.cam.ac.uk.,Vaccine Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.,Molecular Biology Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892; and.,Biomolecular Engineering Research Institute, 6-2-3 Furuedai, Suita, Osaka 565-0874, Japan.,Department of Biochemistry, University of Cambridge, Cambridge, UK.,Department of Pharmacology, University of Cambridge, Cambridge CB2 1PD, UK.,Department of Chemistry , The State University of New York Cortland , Cortland , New York 13045 , United States.,Department of Pharmaceutical Sciences, Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, ON M5S 3M2, Canada.,Department for Structural and Computational Biology, Max F. Perutz Laboratories, University of Vienna, 1030, Vienna, Austria.,Centro Nacional de Biotecnología (CSIC), Darwin 3, 28049 Madrid, Spain.,4PKU-IDG/McGovern Institute for Brain Research, Peking University, Beijing, 100871 China.,Istituto Nazionale Biostrutture e Biosistemi , 00136 Rome , Italy.,Beijing Advanced Innovation Center for Structural Biology, Tsinghua-Peking Joint Center for Life Sciences, School of Life Sciences and School of Medicine, Tsinghua University, Beijing 100084, China; Institute of Biology, Westlake Institute for Advanced Study, Westlake University, Shilongshan Road No. 18, Xihu District, Hangzhou 310064, Zhejiang Province, China. Electronic address: shi-lab@tsinghua.edu.cn.,ALBA Synchrotron Light Source, Carrer de la Llum 2-26, Cerdanyola del Vallès, Barcelona 08290, Spain.,Drug Discovery Hub Dortmund (DDHD) am Zentrum für Integrierte Wirkstoffforschung (ZIW), Dortmund, Germany.,Department of Biological Sciences, Columbia University, New York, NY, USA.,Gene Center Munich and Center of Integrated Protein Science-Munich (CiPS-M), Department of Biochemistry, University of Munich, Munich, Germany.,State Key Laboratory of Respiratory Disease, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, PR China.,Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, TX, USA.,Department of Biosciences, Durham University, Science Laboratories, South Road, Durham, DH1 3LE, U.K.,KNU Institute for Microorganisms, Kyungpook National University, Daegu 41566, Republic of Korea.,Centro di Biologia Integrata - CIBIO , Università di Trento , 38123 Povo , Trento , Italy.,Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232, USA.,From the Molecular Biology and s-shuman@ski.mskcc.org.,Departments of Biochemistry and Molecular Genetics, MaRS Centre, West Tower, Floor 16, Toronto, ON, M5G 1M1, Canada.,Department of Biochemistry and Molecular Biology, University of British Columbia, Vancouver, BC V6T 1Z3, Canada; Department of Chemistry, University of British Columbia, Vancouver, BC V6T 1Z1, Canada.,Department of Chemistry, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.,Biochemistry Department, School of Biomedical Sciences, University of Otago, P.O. Box 56, 710 Cumberland Street, Dunedin 9054, New Zealand. peter.mace@otago.ac.nz.,Department of Microbiology and Physiological Systems, University of Massachusetts Medical School, Worcester, United States.,Department of Biochemistry, 1959 NE Pacific Street, Seattle, WA 98195, USA.,Laboratory of Molecular Immunology and Howard Hughes Medical Institute, The Rockefeller University, New York, NY 10065, USA.,Boehringer Ingelheim RCV GmbH & Co KG, Dr. Boehringer Gasse 5-11, 1120 Vienna, Austria.,Department of Biochemistry & Molecular Biology, University of Georgia, Athens, GA 30602, USA.,Biology Department, University of Maryland, College Park, MD 20742.,Centre for HIV and STIs, National Institute for Communicable Diseases (NICD), of the National Health Laboratory Service (NHLS), Johannesburg, 2131, South Africa.,Laboratory for Marine Drugs and Bioproducts of Qingdao National Laboratory for Marine Science and Technology, Qingdao, 266237, China. xzhmao@ouc.edu.cn.,Department of Plant and Microbial Biology, University of California Berkeley, Berkeley, CA, 94720, USA.,School of Chemical and Biomolecular Engineering , Georgia Institute of Technology , Atlanta , Georgia 30332 , United States.,Department of Life Sciences, Imperial College, London, SW7 2AZ, UK. h.low@imperial.ac.uk.,Graduate School of Pharmaceutical Sciences, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo 113-0033, Japan. Electronic address: umeji@mol.f.u-tokyo.ac.jp.,the Faculty of Agriculture, Niigata University, Niigata 950-2181, Japan.,Vaccine Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892; suiy@mail.nih.gov.,Soehngen Institute for Anaerobic Microbiology, Nijmegen, The Netherlands.,Department of Molecular Gastrointestinal Oncology, Ruhr-University Bochum, Bochum, Germany.,UCB/Beryllium Discovery, 98110, 7869 NE Day Road West, Bainbridge Island, WA, USA. jan.abendroth@ucb.com.,Physik Department E22, Technische Universität München, 85748 Garching, Germany; mrief@ph.tum.de gabriel.zoldak@upjs.sk.,Division of Structural Biology, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan.,Program in Molecular Medicine, Hospital for Sick Children Research Institute, Toronto, ON M5G 0A4, Canada.,Stanford Synchrotron Radiation Lightsource, SLAC National Accelerator Laboratory, Menlo Park, CA, 94025, USA.,School of Life Sciences, Anhui University, Hefei, Anhui, People's Republic of China.,Department of Virology and Microbiology, Centro de Biología Molecular "Severo Ochoa" (CSIC-UAM), Instituto de Biología Molecular "Eladio Viñuela" (CSIC), C. Nicolás Cabrera 1, Universidad Autónoma, Canto Blanco, 28049 Madrid, Spain.,Molecular Biology Consortium, Beamline 4.2.2, Advanced Light Source , Lawrence Berkeley National Laboratory , Berkeley , California 94720 , United States.,Centre for the AIDS Programme of Research in South Africa (CAPRISA), University of KwaZulu-Natal, Durban, 4041, South Africa.,the University of Chinese Academy of Sciences, Beijing 100049, China.,NAICONS Srl., 20139 Milan, Italy.,Molecular Biophysics Unit, Indian Institute of Science, Bangalore, India.,From the Department of Biotechnology, asfushi@mail.ecc.u-tokyo.ac.jp.,RIKEN Center for Biosystems Dynamics Research, Suehiro-cho, Tsurumi-ku, Yokohama 230-0045, Japan.,Department of Structural Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15260.,Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX, USA. Zhijian.Chen@UTSouthwestern.edu.,Department of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, PA, 15260, USA. ptang@pitt.edu.,Department of Chemistry and Pharmacy, Medicinal Chemistry, Friedrich-Alexander-Universität Erlangen-Nürnberg, 91058 Erlangen, Germany; liu_xy@mail.tsinghua.edu.cn bshoichet@gmail.com kobilka@stanford.edu peter.gmeiner@fau.de.,Department of Pharmacology, University of California San Diego School of Medicine, La Jolla, CA 92093.,Division of Biology and Bioengineering, California Institute of Technology, Pasadena, CA 91125; houk@chem.ucla.edu sbjkan@caltech.edu frances@cheme.caltech.edu.,Discovery Therapeutics, US Drug Discovery, Shire Pharmaceuticals, Cambridge, MA 02142.,Department of Molecular and Cellular Biochemistry, University of Kentucky, Lexington, KY 40536.,Center for Integrative Chemical Biology and Drug Discovery, Division of Chemical Biology and Medicinal Chemistry, Eshelman School of Pharmacy , University of North Carolina at Chapel Hill , Chapel Hill , North Carolina 27599 , United States.,State Key Laboratory of Microbial Metabolism, Shanghai Jiao-Tong University, Shanghai, China.,Rega Institute and Department of Microbiology and Immunology, KU Leuven, 3000 Leuven, Belgium. Electronic address: kalyan.das@kuleuven.be.,College of Pharmacy, Chung-Ang University,84 Heukseok-ro, Dongjak, Seoul 06974, Republic of Korea.,Ludwig Institute for Cancer Research , Nuffield Department of Clinical Medicine , University of Oxford , Oxford OX3 7DQ , UK.,Department of Biochemistry and Biotechnology, University of Thessaly, Biopolis, 41500 Larissa, Greece.,Department of Structural Cell Biology, Max Planck Institute of Biochemistry, Munich, Germany.,the Advanced Science Research Center, Okayama University, 3-1-1 Tsushima-Naka, Kita-ku, Okayama 700-8530, Japan.,National Center for Global Health and Medicine Research Institute (NCGM), Tokyo, 162-8655, Japan; Faculty of Pharmaceutical Sciences, Sojo University, Kumamoto, 860-0082, Japan.,University of Chinese Academy of Sciences, Beijing, 100049, China.,Graduate School of Pharmaceutical Sciences , Osaka University , 1-6 Yamadaoka , Suita , Osaka 565-0871 , Japan.,Université de Lyon, École Normale Supérieure de Lyon, CNRS, Université Claude Bernard Lyon 1, Laboratoire de Chimie UMR 518, F-69342, Lyon, France.,School of Food Science and Engineering, South China University of Technology, Guangzhou, PR China. Electronic address: yonghw@scut.edu.cn.,Waksman Institute and Department of Chemistry, Rutgers University, Piscataway, NJ 08854, USA. Electronic address: ebright@waksman.rutgers.edu.,Department of Structural Biology, Weizmann Institute of Science, Rehovot, Israel. ron.diskin@weizmann.ac.il.,Molecular Biophysics and Integrated Bioimaging Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720.,Fachbereich Chemie der Philipps Universität , Hans-Meerwein-Strasse, 35032 Marburg, Germany.,Department of Biochemistry, Vanderbilt University, Nashville, TN 37232-0146, USA. Electronic address: stephen.fesik@vanderbilt.edu.,Divisions of Vaccine Research and Clinical Care and Research, Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD 21201, USA; Virology Department, Pasteur Institute of Iran, Tehran, Iran.,Department of Biochemistry and Molecular Biology and Australian Research Council Centre of Excellence in Advanced Molecular Imaging , Monash University , Clayton , Victoria 3800 , Australia.,Department of Applied Biological Science, Faculty of Science and Technology , Tokyo University of Science , 2641 Yamazaki , Noda , Chiba 278-8510 , Japan.,Australian Nuclear Science and Technology Organisation, Lucas Heights, NSW 2234, Australia.,Division of Gastroenterology, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, 75 Francis Street, Boston, MA, 02115, USA.




Macromolecules

Find similar proteins by: Sequence  |  Structure

Entity ID: 1
MoleculeChainsSequence LengthOrganismDetails
ATP-citrate synthase
A, B, C, D
1116Homo sapiensMutation(s): 0 
Gene Names: ACLY
EC: 2.3.3.8
Find proteins for P53396 (Homo sapiens)
Go to Gene View: ACLY
Go to UniProtKB:  P53396
Small Molecules
Ligands 2 Unique
IDChainsName / Formula / InChI Key2D Diagram3D Interactions
ADP
Query on ADP

Download SDF File 
Download CCD File 
A, B, C, D
ADENOSINE-5'-DIPHOSPHATE
C10 H15 N5 O10 P2
XTWYTFMLZFPYCI-KQYNXXCUSA-N
 Ligand Interaction
LBG
Query on LBG

Download SDF File 
Download CCD File 
A, B, C, D
methyl 3-chloro-5-[(4,6-difluoro[1,1'-biphenyl]-3-yl)sulfamoyl]-4-hydroxybenzoate
C20 H14 Cl F2 N O5 S
YSTSHUWHIDBZAK-UHFFFAOYSA-N
 Ligand Interaction
Experimental Data & Validation

Experimental Data

  • Method: ELECTRON MICROSCOPY
  • Resolution: 3.67 Å
  • Aggregation State: PARTICLE 
  • Reconstruction Method: SINGLE PARTICLE 

Structure Validation

View Full Validation Report or Ramachandran Plots



Entry History & Funding Information

Deposition Data

  • Deposited Date: 2019-02-16 
  • Released Date: 2019-04-17 
  • Deposition Author(s): Wei, J., Tong, L.

Funding OrganizationLocationGrant Number
Other privateUnited StatesNimbus Therapeutics
Other privateUnited StatesSimons Foundation (349247)
National Institutes of Health/National Institute of General Medical SciencesUnited StatesGM103310
Other governmentUnited StatesNYSTAR

Revision History 

  • Version 1.0: 2019-04-17
    Type: Initial release
  • Version 1.1: 2019-05-08
    Type: Data collection, Database references