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Updated: Aug 16, 2026

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Published on: March 28, 2017
Structures of human microsomal cytochrome P450 2A6 complexed with coumarin and methoxsalen
Jason K Yano1, Mei-Hui Hsu, Keith J Griffin
1Department of Molecular and Experimental Medicine, Scripps Research Institute, La Jolla, California 92037, USA.
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.
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