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Evolutionary Relationship Of Substrate Recognition Sites With Protein Functions Of Mammalian Cytochrome P450 Enzymes

Posted on:2016-05-21Degree:MasterType:Thesis
Country:ChinaCandidate:J X WangFull Text:PDF
GTID:2310330503994695Subject:Biology
Abstract/Summary:PDF Full Text Request
Cytochrome P450(CYPs) enzymes exist in almost all kinds of species, which descended from a single common ancestor via gene duplication and constitute a large superfamily through the expansion with evolutionary diversity. As a kind of hemeprotein which containing a heme cofactor, cytochrome P450 catalyze the substrates like monooxygenases. Besides the endogenous metabolism like cholesterol, steroids or other lipids, CYPs are also involved in the xenobiotics biodegradation and metabolism with function diversity, especially the members of human CYP1~4 families which play important roles in drug metabolism. Seven active subfamilies(CYP2A, CYP2 C, CYP2 D, CYP2 E, CYP2 J, CYP3 A and CYP4F) were found by sequence alignment and annotation for 644 CYPs of 11 mammals, which have a strong trend to expand or shrink on the scale of family size during the evolution. In contrast, the family size of non-CYP1~4 families remains nearly the same among mammals. Base on the secondary structure alignment and the calculation of evolutionary rates, six substrate recognition sites(SRSs) in CYP1~4 families, especially in seven active subfamilies, are significantly higher than those in the other families, which can explain the relationship between the CYP1~4 members and the xenobiotics. As for the six substrate recognition sites of CYPs, SRS1~3 have faster evolutionary rates than SRS4~6, which indicates that SRS1~3 are more likely to determine the functions CYPs obtained during the enzyme evolution. With the comprehensive analysis of CYPs' sequences, structures and functions, the mode of its evolutionary pattern and enzyme-substrate recognition/binding pattern can be well illustrated.
Keywords/Search Tags:Cytochrome P450, Family Size, Active Subfamily, Substrate Recognition Sites, Evolutionary Rate
PDF Full Text Request
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