1Z10

Crystal Structure of Human Microsomal P450 2A6 with Coumarin Bound

Summary for 1Z10

• Entry DOI: 10.2210/pdb1z10/pdb
• Related: 1PQ2 1R9O 1TQN 1Z11
• Descriptor: cytochrome P450, family 2, subfamily A, polypeptide 6, PROTOPORPHYRIN IX CONTAINING FE, COUMARIN, ... (5 entities in total)
• Functional Keywords: cyp2a6, p450 2a6, p450, monooxygenase, drug metabolizing enzyme, coumarin 7-hydroxylase, nicotine oxidase, oxidoreductase, heme
• Biological source: Homo sapiens (human)
• Cellular location: Endoplasmic reticulum membrane; Peripheral membrane protein: P11509
• Total number of polymer chains: 4
• Total formula weight: 221829.16

Authors

Yano, J.K.,Hsu, M.H.,Griffin, K.J.,Stout, C.D.,Johnson, E.F. (deposition date: 2005-03-02, release date: 2005-08-16, Last modification date: 2023-08-23)

Primary citation

Yano, J.K.,Hsu, M.H.,Griffin, K.J.,Stout, C.D.,Johnson, E.F.
Structures of human microsomal cytochrome P450 2A6 complexed with coumarin and methoxsalen
Nat.Struct.Mol.Biol., 12:822-823, 2005

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.

PubMed: 16086027
DOI: 10.1038/nsmb971

Experimental method

X-RAY DIFFRACTION (1.9 Å)