1W0F

Crystal structure of human cytochrome P450 3A4


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.65 Å
  • R-Value Free: 0.303 
  • R-Value Work: 0.239 

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This is version 1.3 of the entry. See complete history


Literature

Crystal Structures of Human Cytochrome P450 3A4 Bound to Metyrapone and Progesterone

Williams, P.A.Cosme, J.Vinkovic, D.M.Ward, A.Angove, H.C.Day, P.J.Vonrhein, C.Tickle, I.J.Jhoti, H.

(2004) Science 305: 683

  • DOI: https://doi.org/10.1126/science.1099736
  • Primary Citation of Related Structures:  
    1W0E, 1W0F, 1W0G

  • PubMed Abstract: 

    Cytochromes P450 (P450s) metabolize a wide range of endogenous compounds and xenobiotics, such as pollutants, environmental compounds, and drug molecules. The microsomal, membrane-associated, P450 isoforms CYP3A4, CYP2D6, CYP2C9, CYP2C19, CYP2E1, and CYP1A2 are responsible for the oxidative metabolism of more than 90% of marketed drugs. Cytochrome P450 3A4 (CYP3A4) metabolizes more drug molecules than all other isoforms combined. Here we report three crystal structures of CYP3A4: unliganded, bound to the inhibitor metyrapone, and bound to the substrate progesterone. The structures revealed a surprisingly small active site, with little conformational change associated with the binding of either compound. An unexpected peripheral binding site is identified, located above a phenylalanine cluster, which may be involved in the initial recognition of substrates or allosteric effectors.


  • Organizational Affiliation

    Astex Technology, 436 Cambridge Science Park, Milton Road, Cambridge, CB4 0QA, UK.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
CYTOCHROME P450 3A4485Homo sapiensMutation(s): 0 
EC: 1.14.13.67 (PDB Primary Data), 1.14.14.1 (PDB Primary Data)
UniProt & NIH Common Fund Data Resources
Find proteins for P08684 (Homo sapiens)
Explore P08684 
Go to UniProtKB:  P08684
PHAROS:  P08684
GTEx:  ENSG00000160868 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP08684
Sequence Annotations
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  • Reference Sequence
Small Molecules
Ligands 2 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
HEM
Query on HEM

Download Ideal Coordinates CCD File 
C [auth A]PROTOPORPHYRIN IX CONTAINING FE
C34 H32 Fe N4 O4
KABFMIBPWCXCRK-RGGAHWMASA-L
STR
Query on STR

Download Ideal Coordinates CCD File 
B [auth A]PROGESTERONE
C21 H30 O2
RJKFOVLPORLFTN-LEKSSAKUSA-N
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.65 Å
  • R-Value Free: 0.303 
  • R-Value Work: 0.239 
  • Space Group: I 2 2 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 77.41α = 90
b = 101.51β = 90
c = 128.66γ = 90
Software Package:
Software NamePurpose
CNXrefinement
MOSFLMdata reduction
SCALAdata 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: 2004-07-22
    Type: Initial release
  • Version 1.1: 2011-05-08
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Version format compliance
  • Version 1.3: 2023-12-13
    Changes: Data collection, Database references, Derived calculations, Other, Refinement description