1Z11

Crystal Structure of Human Microsomal P450 2A6 with Methoxsalen Bound


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.05 Å
  • R-Value Free: 0.261 
  • R-Value Work: 0.219 
  • R-Value Observed: 0.221 

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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
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
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  • Reference Sequence
Small Molecules
Binding Affinity Annotations 
IDSourceBinding Affinity
8MO BindingDB:  1Z11 Ki: min: 40, max: 1900 (nM) from 4 assay(s)
Kd: min: 1600, max: 1.10e+4 (nM) from 2 assay(s)
Binding MOAD:  1Z11 Kd: 1900 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.05 Å
  • R-Value Free: 0.261 
  • R-Value Work: 0.219 
  • R-Value Observed: 0.221 
  • Space Group: P 1 21 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 70.66α = 90
b = 159.03β = 92
c = 103.88γ = 90
Software Package:
Software NamePurpose
HKL-2000data collection
SCALEPACKdata scaling
AMoREphasing
CNSrefinement
HKL-2000data reduction

Structure Validation

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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: Version format compliance
  • Version 1.3: 2023-08-23
    Changes: Data collection, Database references, Derived calculations, Refinement description