Structural divergence and adaptive evolution in mammalian cytochromes P4502C
Structural divergence and adaptive evolution in mammalian cytochromes P4502C
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DOI：
10.1016/j.gene.2006.08.017
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发表时间：
2007-01-31
期刊：
影响因子：
3.5
通讯作者：
Ramos, Maria Joao
中科院分区：
文献类型：
--
作者：
da Fonseca, Rute R.;Antunes, Agostinho;Ramos, Maria Joao
细胞色素P450（CYP）是一个酶超家族，参与各种生理功能，包括药物和食物中致癌化合物的代谢，对人类健康非常重要。CYP可能会根据环境中可获得的外源性化合物的高度多样性而扩大或改变底物特异性，这表明它们的代谢功能可能处于适应性进化之下。我们评估了药物代谢CYP2家族哺乳动物基因的功能差异和选择特征的存在。13个网站被发现是功能上的分歧和8个被发现是根据强阳性选择发生在重要的功能域，即在基板入口通道和活性位点内。我们的研究结果提供了深入了解CYP的进化和酶底物特异性多样化的分子适应的作用。(c)2006 Elsevier B.V.保留所有权利。
Cytochromes P450 (CYPs) comprise a superfamily of enzymes involved in various physiological functions, including the metabolism of drugs and carcinogenic compounds present in food, making them of great importance for human health. The possibility that CYPs could be broadening or changing substrate specificity in accordance to the high diversity of xenobiotics compounds environmentally available suggests that their metabolic function could be under adaptive evolution. We evaluated the existence of functional divergence and signatures of selection on mammalian genes from the drug-metabolizing CYP2 family. Thirteen of the sites found to be functionally divergent and the eight found to be under strong positive selection occurred in important functional domains, namely on the substrate entrance channel and within the active site. Our results provide insight into CYPs evolution and the role of molecular adaptation in enzyme substrate-specificity diversification. (c) 2006 Elsevier B.V. All rights reserved.