Structures of human microsomal cytochrome P450 2A6 complexed with coumarin and methoxsalen.
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Yano JK, Hsu MH, Griffin KJ, Stout CD, Johnson EF
Structures of human microsomal cytochrome P450 2A6 complexed with coumarin and methoxsalen.
Nat Struct Mol Biol. 2005 Sep;12(9):822-3. Epub 2005 Aug 7.
- PubMed ID
- 16086027 [ View in 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.