6N48

Structure of beta2 adrenergic receptor bound to BI167107, Nanobody 6B9, and a positive allosteric modulator


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 3.20 Å
  • R-Value Free: 0.274 
  • R-Value Work: 0.251 
  • R-Value Observed: 0.253 

wwPDB Validation   3D Report Full Report

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This is version 1.3 of the entry. See complete history


Literature

Mechanism of beta2AR regulation by an intracellular positive allosteric modulator.

Liu, X.Masoudi, A.Kahsai, A.W.Huang, L.Y.Pani, B.Staus, D.P.Shim, P.J.Hirata, K.Simhal, R.K.Schwalb, A.M.Rambarat, P.K.Ahn, S.Lefkowitz, R.J.Kobilka, B.

(2019) Science 364: 1283-1287

  • DOI: https://doi.org/10.1126/science.aaw8981
  • Primary Citation of Related Structures:  
    6N48

  • PubMed Abstract: 

    Drugs targeting the orthosteric, primary binding site of G protein-coupled receptors are the most common therapeutics. Allosteric binding sites, elsewhere on the receptors, are less well-defined, and so less exploited clinically. We report the crystal structure of the prototypic β 2 -adrenergic receptor in complex with an orthosteric agonist and compound-6FA, a positive allosteric modulator of this receptor. It binds on the receptor's inner surface in a pocket created by intracellular loop 2 and transmembrane segments 3 and 4, stabilizing the loop in an α-helical conformation required to engage the G protein. Structural comparison explains the selectivity of the compound for β 2 - over the β 1 -adrenergic receptor. Diversity in location, mechanism, and selectivity of allosteric ligands provides potential to expand the range of receptor drugs.


  • Organizational Affiliation

    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.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Endolysin,Beta-2 adrenergic receptor,Beta-2 adrenergic receptor chimera469Enterobacteria phage RB59Homo sapiensMutation(s): 6 
Gene Names: eRB59_126ADRB2ADRB2RB2AR
EC: 3.2.1.17
Membrane Entity: Yes 
UniProt & NIH Common Fund Data Resources
Find proteins for P07550 (Homo sapiens)
Explore P07550 
Go to UniProtKB:  P07550
GTEx:  ENSG00000169252 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP07550
Sequence Annotations
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  • Reference Sequence
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
Camelid Antibody Fragment120CamelidaeMutation(s): 0 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 3 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
KBY
Query on KBY

Download Ideal Coordinates CCD File 
E [auth A]N-[(3R)-4-(4-tert-butylphenyl)-3-({2-[(4-methoxyphenyl)sulfanyl]-5-[methyl(propan-2-yl)sulfamoyl]benzene-1-carbonyl}amino)butanoyl]glycine
C34 H43 N3 O7 S2
POBZRCRFILRWTQ-RUZDIDTESA-N
P0G
Query on P0G

Download Ideal Coordinates CCD File 
C [auth A]8-[(1R)-2-{[1,1-dimethyl-2-(2-methylphenyl)ethyl]amino}-1-hydroxyethyl]-5-hydroxy-2H-1,4-benzoxazin-3(4H)-one
C21 H26 N2 O4
NWQXBEWHTDRJIP-KRWDZBQOSA-N
1WV
Query on 1WV

Download Ideal Coordinates CCD File 
D [auth A](2S)-2,3-dihydroxypropyl (7Z)-tetradec-7-enoate
C17 H32 O4
LVBAGTJIDOCNIJ-INIZCTEOSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
P0G BindingDB:  6N48 EC50: 0.1 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 3.20 Å
  • R-Value Free: 0.274 
  • R-Value Work: 0.251 
  • R-Value Observed: 0.253 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 49.15α = 90
b = 66.06β = 90
c = 303.51γ = 90
Software Package:
Software NamePurpose
PHENIXrefinement
XDSdata reduction
XSCALEdata scaling
PHENIXphasing

Structure Validation

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Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2019-06-26
    Type: Initial release
  • Version 1.1: 2019-07-03
    Changes: Data collection, Database references
  • Version 1.2: 2019-07-10
    Changes: Data collection, Database references
  • Version 1.3: 2023-10-11
    Changes: Data collection, Database references, Refinement description