Structural divergence and adaptive evolution in mammalian cytochromes P4502C

• Type: Article in International Scientific Journal
• Date: 2007

Authors

Rute R da Fonseca (Author) Other; Agostinho Antunes (Author) REIT; Andre Melo (Author) FCUP; Maria Joao Ramos (Author) FCUP

Journal

Title: Gene

Vol. 387

Pages: 58-66

ISSN: 0378-1119

Publisher: Elsevier

Indexing

ISI Web of Knowledge - 24 Citations

Scopus - 27 Citations

Scientific classification

FOS: Natural sciences > Earth and related Environmental sciences

Other information

Authenticus ID: P-004-C6K

DOI: 10.1016/j.gene.2006.08.017

Abstract (EN): 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.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 9