6HP0

Complex of Neuraminidase from H1N1 Influenza Virus in Complex with Oseltamivir Triazol Derivative


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.88 Å
  • R-Value Free: 0.222 
  • R-Value Work: 0.185 

wwPDB Validation 3D Report Full Report


This is version 1.1 of the entry. See complete history

Literature

Investigation of flexibility of neuraminidase 150-loop using tamiflu derivatives in influenza A viruses H1N1 and H5N1.

Zima, V.Albinana, C.B.Rojikova, K.Pokorna, J.Pachl, P.Rezacova, P.Hudlicky, J.Navratil, V.Majer, P.Konvalinka, J.Kozisek, M.Machara, A.

(2019) Bioorg.Med.Chem. 27: 2935-2947

  • DOI: 10.1016/j.bmc.2019.05.024

  • PubMed Abstract: 
  • This study focuses on design, synthesis and in vitro evaluation of inhibitory potency of two series of sialylmimetic that target an exosite ("150-cavity") adjacent to the active site of influenza neuraminidases from A/California/07/2009 (H1N1) pandem ...

    This study focuses on design, synthesis and in vitro evaluation of inhibitory potency of two series of sialylmimetic that target an exosite ("150-cavity") adjacent to the active site of influenza neuraminidases from A/California/07/2009 (H1N1) pandemic strain and A/chicken/Nakorn-Patom/Thailand/CU-K2-2004 (H5N1). The structure-activity analysis as well as 3-D structure of the complex of parental compound with the pandemic neuraminidase p09N1 revealed high flexibility of the 150-cavity towards various modification of the neuraminidase inhibitors. Furthermore, our comparison of two methods for inhibition constant determination performed at slightly different pH values suggest that the experimental conditions of the measurement could dramatically influence the outcome of the analysis in the compound-dependent manner. Therefore, previously reported K i values determined at non-physiological pH should be carefully scrutinized.


    Organizational Affiliation

    Department of Organic Chemistry, Faculty of Science, Charles University, Hlavova 8, 128 00 Prague 2, Czech Republic; Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences, Gilead Sciences and IOCB Research Center, Flemingovo n. 2, 166 10 Prague 6, Czech Republic. Electronic address: ales.machara@uochb.cas.cz.,Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences, Gilead Sciences and IOCB Research Center, Flemingovo n. 2, 166 10 Prague 6, Czech Republic; First Faculty of Medicine, Charles University, Kateřinská 1660/32, 121 08, Prague, Czech Republic.,Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences, Gilead Sciences and IOCB Research Center, Flemingovo n. 2, 166 10 Prague 6, Czech Republic; Institute of Molecular Genetics, Academy of Sciences of the Czech Republic, Vídeňská 1083, 140 00 Prague 4, Czech Republic.,Department of Organic Chemistry, Faculty of Science, Charles University, Hlavova 8, 128 00 Prague 2, Czech Republic; Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences, Gilead Sciences and IOCB Research Center, Flemingovo n. 2, 166 10 Prague 6, Czech Republic.,Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences, Gilead Sciences and IOCB Research Center, Flemingovo n. 2, 166 10 Prague 6, Czech Republic.,Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences, Gilead Sciences and IOCB Research Center, Flemingovo n. 2, 166 10 Prague 6, Czech Republic; Department of Biochemistry, Faculty of Science, Charles University, Hlavova 8, 128 00 Prague 2, Czech Republic.




Macromolecules

Find similar proteins by: Sequence  |  Structure

Entity ID: 1
MoleculeChainsSequence LengthOrganismDetails
Neuraminidase
A, B, C, D
388Influenza A virusMutation(s): 0 
Gene Names: NA
EC: 3.2.1.18
Find proteins for C6KP13 (Influenza A virus)
Go to UniProtKB:  C6KP13
Small Molecules
Ligands 8 Unique
IDChainsName / Formula / InChI Key2D Diagram3D Interactions
GJT
Query on GJT

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Download CCD File 
A, B, C, D
(3~{R},4~{R},5~{S})-4-acetamido-5-[4-(hydroxymethyl)-1,2,3-triazol-1-yl]-3-pentan-3-yloxy-cyclohexene-1-carboxylic acid
C17 H26 N4 O5
IPVDZUUVRPUAMB-ARFHVFGLSA-N
 Ligand Interaction
CA
Query on CA

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A, B, C, D
CALCIUM ION
Ca
BHPQYMZQTOCNFJ-UHFFFAOYSA-N
 Ligand Interaction
MAN
Query on MAN

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C
ALPHA-D-MANNOSE
C6 H12 O6
WQZGKKKJIJFFOK-PQMKYFCFSA-N
 Ligand Interaction
FUC
Query on FUC

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A, B, C, D
ALPHA-L-FUCOSE
C6 H12 O5
SHZGCJCMOBCMKK-SXUWKVJYSA-N
 Ligand Interaction
EDO
Query on EDO

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A, B, C, D
1,2-ETHANEDIOL
ETHYLENE GLYCOL
C2 H6 O2
LYCAIKOWRPUZTN-UHFFFAOYSA-N
 Ligand Interaction
BMA
Query on BMA

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C
BETA-D-MANNOSE
C6 H12 O6
WQZGKKKJIJFFOK-RWOPYEJCSA-N
 Ligand Interaction
PGE
Query on PGE

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D
TRIETHYLENE GLYCOL
C6 H14 O4
ZIBGPFATKBEMQZ-UHFFFAOYSA-N
 Ligand Interaction
NAG
Query on NAG

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A, B, C, D
N-ACETYL-D-GLUCOSAMINE
C8 H15 N O6
OVRNDRQMDRJTHS-FMDGEEDCSA-N
 Ligand Interaction
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.88 Å
  • R-Value Free: 0.222 
  • R-Value Work: 0.185 
  • Space Group: P 1 21 1
Unit Cell:
Length (Å)Angle (°)
a = 85.842α = 90.00
b = 126.861β = 93.93
c = 96.906γ = 90.00
Software Package:
Software NamePurpose
XDSdata scaling
REFMACrefinement
XDSdata reduction
MOLREPphasing

Structure Validation

View Full Validation Report or Ramachandran Plots



Entry History & Funding Information

Deposition Data

  • Deposited Date: 2018-09-19 
  • Released Date: 2019-09-11 
  • Deposition Author(s): Pachl, P., Pokorna, J.

Funding OrganizationLocationGrant Number
Ministry of Education (Czech Republic)Czech RepublicInterBioMed LO1302

Revision History 

  • Version 1.0: 2019-09-11
    Type: Initial release
  • Version 1.1: 2019-09-18
    Type: Data collection, Database references