Structural divergence and adaptive evolution in mammalian cytochromes P4502C

• Tipo: Artigo em Revista Científica Internacional
• Data: 2007

Autores

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

Revista

Título: Gene

Vol. 387

Páginas: 58-66

ISSN: 0378-1119

Editora: Elsevier

Indexação

ISI Web of Knowledge - 24 Citações

Scopus - 27 Citações

Classificação Científica

FOS: Ciências exactas e naturais > Ciências da terra e ciências do ambiente

Outras Informações

ID Authenticus: 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.

Idioma: Inglês

Tipo (Avaliação Docente): Científica

Nº de páginas: 9