Cytochromes P450: a success story.
Cytochromes P450: a success story.
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DOI：
10.1186/gb-2000-1-6-reviews3003
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发表时间：
2000
期刊：
影响因子：
12.3
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中科院分区：
文献类型：
--
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细胞色素P450蛋白是在多种途径中起作用的酶，从碳源同化到激素生物合成。在所有p450中，血红素结合在结构保守的蛋白核心，使它们能够催化碳氢化合物的区域选择性和立体选择性氧化。细胞色素P450蛋白是酶蛋白中最大的超家族之一，因其与一氧化碳结合的450纳米吸收带而命名。P450基因（也称为CYP）几乎存在于所有生物体的基因组中，但它们在植物中的数量激增。它们的氨基酸序列非常多样化，在某些情况下同源性水平低至16%，但它们的结构折叠在整个进化过程中保持不变。p450是血红素硫酸酯蛋白；它们最保守的结构特征与血红素结合和常见的催化性能有关，主要特征是半胱氨酸作为血红素铁的第五（轴向）配体完全保守。典型的p450利用来自NAD(P)H的电子催化分子氧的活化，导致大量底物的区域特异性和立体特异性氧化攻击。p450进行的反应，虽然通常是羟基化，但可以非常多样化，有时令人惊讶。它们有助于重要的过程，如碳源同化、激素和生物体结构成分的生物合成，以及异种生物的致癌和降解。在植物中，化学防御似乎是P450多样化的主要原因。在原核生物中，p450是可溶性蛋白质。在真核生物中，它们通常与内质网或线粒体内膜结合。用于传递NAD(P)H还原等价物的电子载体蛋白随着亚细胞定位的不同而不同。P450酶催化许多在药物代谢或工业上有实际应用的重要反应；因此，它们的经济影响是相当大的。
Cytochrome P450 proteins are enzymes that function in diverse pathways, from carbon source assimilation to hormone biosynthesis. In all P450s, heme is bound in a structurally conserved protein core, allowing them to catalyze regioselective and stereoselective oxidation of hydrocarbons. Cytochrome P450 proteins, named for the absorption band at 450 nm of their carbon-monoxide-bound form, are one of the largest superfamilies of enzyme proteins. The P450 genes (also called CYP) are found in the genomes of virtually all organisms, but their number has exploded in plants. Their amino-acid sequences are extremely diverse, with levels of identity as low as 16% in some cases, but their structural fold has remained the same throughout evolution. P450s are heme-thiolate proteins; their most conserved structural features are related to heme binding and common catalytic properties, the major feature being a completely conserved cysteine serving as fifth (axial) ligand to the heme iron. Canonical P450s use electrons from NAD(P)H to catalyze activation of molecular oxygen, leading to regiospecific and stereospecific oxidative attack of a plethora of substrates. The reactions carried out by P450s, though often hydroxylation, can be extremely diverse and sometimes surprising. They contribute to vital processes such as carbon source assimilation, biosynthesis of hormones and of structural components of living organisms, and also carcinogenesis and degradation of xenobiotics. In plants, chemical defense seems to be a major reason for P450 diversification. In prokaryotes, P450s are soluble proteins. In eukaryotes, they are usually bound to the endoplasmic reticulum or inner mitochondrial membranes. The electron carrier proteins used for conveying reducing equivalents from NAD(P)H differ with subcellular localization. P450 enzymes catalyze many reactions that are important in drug metabolism or that have practical applications in industry; their economic impact is therefore considerable.