1R9O

Crystal Structure of P4502C9 with Flurbiprofen bound


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.00 Å
  • R-Value Free: 0.236 
  • R-Value Work: 0.191 
  • R-Value Observed: 0.194 

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This is version 1.4 of the entry. See complete history


Literature

The Structure of Human Cytochrome P450 2C9 Complexed with Flurbiprofen at 2.0 A Resolution

Wester, M.R.Yano, J.K.Schoch, G.A.Yang, C.Griffin, K.J.Stout, C.D.Johnson, E.F.

(2004) J Biol Chem 279: 35630-35637

  • DOI: https://doi.org/10.1074/jbc.M405427200
  • Primary Citation of Related Structures:  
    1R9O

  • PubMed Abstract: 

    The structure of human P450 2C9 complexed with flurbiprofen was determined to 2.0 A by x-ray crystallography. In contrast to other structurally characterized P450 2C enzymes, 2C5, 2C8, and a 2C9 chimera, the native catalytic domain of P450 2C9 differs significantly in the conformation of the helix F to helix G region and exhibits an extra turn at the N terminus of helix A. In addition, a distinct conformation of the helix B to helix C region allows Arg-108 to hydrogen bond with Asp-293 and Asn-289 on helix I and to interact directly with the carboxylate of flurbiprofen. These interactions position the substrate for regioselective oxidation in a relatively large active site cavity and are likely to account for the high catalytic efficiency exhibited by P450 2C9 for the regioselective oxidation of several anionic non-steroidal anti-inflammatory drugs. The structure provides a basis for interpretation of a number of observations regarding the substrate selectivity of P450 2C9 and the observed effects of mutations on catalysis.


  • Organizational Affiliation

    Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, California 92037, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Cytochrome P450 2C9477Homo sapiensMutation(s): 6 
Gene Names: CYP2C9
EC: 1.14.14.1
Membrane Entity: Yes 
UniProt & NIH Common Fund Data Resources
Find proteins for P11712 (Homo sapiens)
Explore P11712 
Go to UniProtKB:  P11712
PHAROS:  P11712
GTEx:  ENSG00000138109 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP11712
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.00 Å
  • R-Value Free: 0.236 
  • R-Value Work: 0.191 
  • R-Value Observed: 0.194 
  • Space Group: H 3
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 91.047α = 90
b = 91.047β = 90
c = 169.48γ = 120
Software Package:
Software NamePurpose
MOSFLMdata reduction
SCALAdata scaling
AMoREphasing
CNSrefinement
CCP4data scaling

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2004-06-15
    Type: Initial release
  • Version 1.1: 2008-04-29
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Non-polymer description, Version format compliance
  • Version 1.3: 2021-10-27
    Changes: Database references, Derived calculations
  • Version 1.4: 2023-08-23
    Changes: Data collection, Refinement description