1Z10

Crystal Structure of Human Microsomal P450 2A6 with Coumarin Bound


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.90 Å
  • R-Value Free: 0.230 
  • R-Value Work: 0.194 
  • R-Value Observed: 0.196 

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Ligand Structure Quality Assessment 


This is version 1.3 of the entry. See complete history


Literature

Structures of human microsomal cytochrome P450 2A6 complexed with coumarin and methoxsalen

Yano, J.K.Hsu, M.H.Griffin, K.J.Stout, C.D.Johnson, E.F.

(2005) Nat Struct Mol Biol 12: 822-823

  • DOI: https://doi.org/10.1038/nsmb971
  • Primary Citation of Related Structures:  
    1Z10, 1Z11

  • PubMed Abstract: 

    Human microsomal cytochrome P450 2A6 (CYP2A6) contributes extensively to nicotine detoxication but also activates tobacco-specific procarcinogens to mutagenic products. The CYP2A6 structure shows a compact, hydrophobic active site with one hydrogen bond donor, Asn297, that orients coumarin for regioselective oxidation. The inhibitor methoxsalen effectively fills the active site cavity without substantially perturbing the structure. The structure should aid the design of inhibitors to reduce smoking and tobacco-related cancers.


  • Organizational Affiliation

    Department of Molecular and Experimental Medicine, 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, family 2, subfamily A, polypeptide 6
A, B, C, D
476Homo sapiensMutation(s): 0 
Gene Names: CYP2A6
EC: 1.14.14.1
Membrane Entity: Yes 
UniProt & NIH Common Fund Data Resources
Find proteins for P11509 (Homo sapiens)
Explore P11509 
Go to UniProtKB:  P11509
PHAROS:  P11509
GTEx:  ENSG00000255974 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP11509
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 3 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
HEM
Query on HEM

Download Ideal Coordinates CCD File 
E [auth A],
G [auth B],
J [auth C],
L [auth D]
PROTOPORPHYRIN IX CONTAINING FE
C34 H32 Fe N4 O4
KABFMIBPWCXCRK-RGGAHWMASA-L
COU
Query on COU

Download Ideal Coordinates CCD File 
F [auth A],
H [auth B],
K [auth C],
M [auth D]
COUMARIN
C9 H6 O2
ZYGHJZDHTFUPRJ-UHFFFAOYSA-N
GOL
Query on GOL

Download Ideal Coordinates CCD File 
I [auth B]GLYCEROL
C3 H8 O3
PEDCQBHIVMGVHV-UHFFFAOYSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
COU Binding MOAD:  1Z10 Kd: 270 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.90 Å
  • R-Value Free: 0.230 
  • R-Value Work: 0.194 
  • R-Value Observed: 0.196 
  • Space Group: P 1 21 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 70.615α = 90
b = 157.591β = 92.25
c = 103.541γ = 90
Software Package:
Software NamePurpose
HKL-2000data collection
SCALEPACKdata scaling
AMoREphasing
CNSrefinement
HKL-2000data reduction

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2005-08-16
    Type: Initial release
  • Version 1.1: 2008-04-30
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Non-polymer description, Version format compliance
  • Version 1.3: 2023-08-23
    Changes: Data collection, Database references, Derived calculations, Refinement description