Yano Jason K, Hsu Mei-Hui, Griffin Keith J, Stout C David, Johnson Eric F
Department of Molecular and Experimental Medicine, Scripps Research Institute, La Jolla, California 92037, USA.
Nat Struct Mol Biol. 2005 Sep;12(9):822-3. doi: 10.1038/nsmb971. Epub 2005 Aug 7.
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.
人类微粒体细胞色素P450 2A6（CYP2A6）在尼古丁解毒过程中发挥着重要作用，但同时也会将烟草特有的前致癌物激活为诱变产物。CYP2A6的结构显示出一个紧凑的疏水活性位点，其中有一个氢键供体Asn297，它将香豆素定向进行区域选择性氧化。抑制剂甲氧沙林能有效填充活性位点腔，而基本不会干扰结构。该结构应有助于设计抑制剂以减少吸烟及与烟草相关的癌症。
