Structures of human microsomal cytochrome P450 2A6 complexed with coumarin and methoxsalen
Structures of human microsomal cytochrome P450 2A6 complexed with coumarin and methoxsalen
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DOI：
10.1038/nsmb971
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发表时间：
2005-09-01
影响因子：
16.8
通讯作者：
Johnson, EF
中科院分区：
文献类型：
--
作者：
Yano, JK;Hsu, MH;Johnson, EF
人类微粒体细胞色素P450 2A6 （CYP2A6）广泛参与尼古丁解毒，但也激活烟草特异性致癌原致突变产物。CYP2A6结构显示一个紧凑的疏水活性位点，具有一个氢键供体Asn297，定向香豆素进行区域选择性氧化。甲氧沙伦抑制剂有效地填充活性位点空腔，而不会实质上扰乱结构。这种结构应该有助于设计抑制剂来减少吸烟和与烟草相关的癌症。
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.