1Z11

Crystal Structure of Human Microsomal P450 2A6 with Methoxsalen Bound

PDB DOI: https://doi.org/10.2210/pdb1Z11/pdb

Classification: OXIDOREDUCTASE
Organism(s): Homo sapiens
Expression System: Escherichia coli
Mutation(s): No

Deposited: 2005-03-02 Released: 2005-08-16
Deposition Author(s): Yano, J.K., Hsu, M.H., Griffin, K.J., Stout, C.D., Johnson, E.F.

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

Starting Model: experimental
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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

PubMed: 16086027 Search on PubMed
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.

Macromolecule Content

Total Structure Weight: 222.02 kDa
Atom Count: 15,779
Modelled Residue Count: 1,859
Deposited Residue Count: 1,904
Unique protein chains: 1

Macromolecules

Find similar proteins by:

(by identity cutoff) | 3D Structure

Entity ID: 1
Molecule	Chains	Sequence Length	Organism	Details	Image
cytochrome P450, family 2, subfamily A, polypeptide 6	A, B, C, D	476	Homo sapiens	Mutation(s): 0 Gene Names: CYP2A6 EC: 1.14.14.1 (PDB Primary Data), 1.14.14 (UniProt)
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 Clusters	30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt Group	P11509
Sequence Annotations Expand
Reference Sequence

Small Molecules

Ligands 2 Unique
ID	Chains	Name / Formula / InChI Key	2D Diagram	3D Interactions
HEM Query on HEM Download Ideal Coordinates CCD File SDF format, chain E [auth A] SDF format, chain I [auth C] SDF format, chain G [auth B] SDF format, chain K [auth D] MOL2 format, chain E [auth A] MOL2 format, chain I [auth C] MOL2 format, chain G [auth B] MOL2 format, chain K [auth D] mmCIF format, chain E [auth A] mmCIF format, chain I [auth C] mmCIF format, chain G [auth B] mmCIF format, chain K [auth D]	E [auth A], G [auth B], I [auth C], K [auth D]	PROTOPORPHYRIN IX CONTAINING FE C₃₄ H₃₂ Fe N₄ O₄ KABFMIBPWCXCRK-RGGAHWMASA-L		Interactions Focus chain E [auth A] Focus chain G [auth B] Focus chain I [auth C] Focus chain K [auth D] Interactions & Density Focus chain E [auth A] Focus chain G [auth B] Focus chain I [auth C] Focus chain K [auth D]
8MO Query on 8MO Download Ideal Coordinates CCD File SDF format, chain F [auth A] SDF format, chain H [auth B] SDF format, chain J [auth C] SDF format, chain L [auth D] MOL2 format, chain F [auth A] MOL2 format, chain H [auth B] MOL2 format, chain J [auth C] MOL2 format, chain L [auth D] mmCIF format, chain F [auth A] mmCIF format, chain H [auth B] mmCIF format, chain J [auth C] mmCIF format, chain L [auth D]	F [auth A], H [auth B], J [auth C], L [auth D]	METHOXSALEN C₁₂ H₈ O₄ QXKHYNVANLEOEG-UHFFFAOYSA-N		Interactions Focus chain F [auth A] Focus chain H [auth B] Focus chain J [auth C] Focus chain L [auth D] Interactions & Density Focus chain F [auth A] Focus chain H [auth B] Focus chain J [auth C] Focus chain L [auth D]

Binding Affinity Annotations
ID	Source	Binding Affinity
8MO	BindingDB: 1Z11	Ki: min: 40, max: 1900 (nM) from 6 assay(s)
		Kd: min: 1600, max: 1.10e+4 (nM) from 2 assay(s)
		IC50: 460 (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 = 70.66	α = 90
b = 159.03	β = 92
c = 103.88	γ = 90

Software Package:

Software Name	Purpose
HKL-2000	data collection
SCALEPACK	data scaling
AMoRE	phasing
CNS	refinement
HKL-2000	data reduction

Structure Validation

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Ligand Structure Quality Assessment

Entry History

Deposition Data

Released Date: 2005-08-16

Deposition Author(s):

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