1EQG

THE 2.6 ANGSTROM MODEL OF OVINE COX-1 COMPLEXED WITH IBUPROFEN


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.61 Å
  • R-Value Free: 0.250 
  • R-Value Work: 0.223 
  • R-Value Observed: 0.223 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.6 of the entry. See complete history


Literature

Structural analysis of NSAID binding by prostaglandin H2 synthase: time-dependent and time-independent inhibitors elicit identical enzyme conformations.

Selinsky, B.S.Gupta, K.Sharkey, C.T.Loll, P.J.

(2001) Biochemistry 40: 5172-5180

  • DOI: https://doi.org/10.1021/bi010045s
  • Primary Citation of Related Structures:  
    1EQG, 1EQH, 1HT5, 1HT8

  • PubMed Abstract: 

    Nonsteroidal antiinflammatory drugs (NSAIDs) block prostanoid biosynthesis by inhibiting prostaglandin H(2) synthase (EC 1.14.99.1). NSAIDs are either rapidly reversible competitive inhibitors or slow tight-binding inhibitors of this enzyme. These different modes of inhibition correlate with clinically important differences in isoform selectivity. Hypotheses have been advanced to explain the different inhibition kinetics, but no structural data have been available to test them. We present here crystal structures of prostaglandin H(2) synthase-1 in complex with the inhibitors ibuprofen, methyl flurbiprofen, flurbiprofen, and alclofenac at resolutions ranging from 2.6 to 2.75 A. These structures allow direct comparison of enzyme complexes with reversible competitive inhibitors (ibuprofen and methyl flurbiprofen) and slow tight-binding inhibitors (alclofenac and flurbiprofen). The four inhibitors bind to the same site and adopt similar conformations. In all four complexes, the enzyme structure is essentially unchanged, exhibiting only minimal differences in the inhibitor binding site. These results argue strongly against hypotheses that explain the difference between slow tight-binding and fast reversible competitive inhibition by invoking global conformational differences or different inhibitor binding sites. Instead, they suggest that the different apparent modes of NSAID binding may result from differences in the speed and efficiency with which inhibitors can perturb the hydrogen bonding network around Arg-120 and Tyr-355.


  • Organizational Affiliation

    Department of Chemistry, Villanova University, Pennsylvania 19085, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
PROSTAGLANDIN H2 SYNTHASE-1
A, B
580Ovis ariesMutation(s): 0 
EC: 1.14.99.1
UniProt
Find proteins for P05979 (Ovis aries)
Explore P05979 
Go to UniProtKB:  P05979
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP05979
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 4 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
HEM
Query on HEM

Download Ideal Coordinates CCD File 
J [auth A],
R [auth B]
PROTOPORPHYRIN IX CONTAINING FE
C34 H32 Fe N4 O4
KABFMIBPWCXCRK-RGGAHWMASA-L
BOG
Query on BOG

Download Ideal Coordinates CCD File 
G [auth A],
H [auth A],
Q [auth B]
octyl beta-D-glucopyranoside
C14 H28 O6
HEGSGKPQLMEBJL-RKQHYHRCSA-N
NAG
Query on NAG

Download Ideal Coordinates CCD File 
C [auth A]
D [auth A]
E [auth A]
F [auth A]
I [auth A]
C [auth A],
D [auth A],
E [auth A],
F [auth A],
I [auth A],
L [auth B],
M [auth B],
N [auth B],
O [auth B],
P [auth B]
2-acetamido-2-deoxy-beta-D-glucopyranose
C8 H15 N O6
OVRNDRQMDRJTHS-FMDGEEDCSA-N
IBP
Query on IBP

Download Ideal Coordinates CCD File 
K [auth A],
S [auth B]
IBUPROFEN
C13 H18 O2
HEFNNWSXXWATRW-JTQLQIEISA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
IBP BindingDB:  1EQG Ki: min: 48, max: 9000 (nM) from 5 assay(s)
IC50: min: 99, max: 7.28e+4 (nM) from 43 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.61 Å
  • R-Value Free: 0.250 
  • R-Value Work: 0.223 
  • R-Value Observed: 0.223 
  • Space Group: I 2 2 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 98.65α = 90
b = 204.99β = 90
c = 221.96γ = 90
Software Package:
Software NamePurpose
DENZOdata reduction
SCALEPACKdata scaling
CNSrefinement
CNSphasing

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2001-04-11
    Type: Initial release
  • Version 1.1: 2008-04-27
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Non-polymer description, Version format compliance
  • Version 1.3: 2018-01-31
    Changes: Advisory, Experimental preparation
  • Version 1.4: 2018-02-28
    Changes: Experimental preparation
  • Version 1.5: 2020-07-29
    Type: Remediation
    Reason: Carbohydrate remediation
    Changes: Data collection, Derived calculations, Structure summary
  • Version 1.6: 2024-03-13
    Changes: Data collection, Database references, Source and taxonomy, Structure summary