Molecular modelling of human CYP2C subfamily enzymes CYP2C9 and CYP2C19: rationalization of substrate specificity and site-directed mutagenesis experiments in the CYP2C subfamily
1998; Taylor & Francis; Volume: 28; Issue: 3 Linguagem: Inglês
10.1080/004982598239542
ISSN1366-5928
AutoresDavid F. Lewis, Maurice Dickins, Richard Weaver, Peter Eddershaw, Peter S. Goldfarb, Michael H. Tarbit,
Tópico(s)Receptor Mechanisms and Signaling
Resumo1. The results of molecular modelling of human CYP2C isozymes, CYP2C9 and CYP2C19, are reported based on an alignment with a bacterial form of the enzyme, CYP102. 2. The three-dimensional structures of the CYP2C enzymes are consistent with known experimental evidence from site-directed mutagenesis, antibody recognition and regiospecificity of substrate metabolism. 3. The variations in substrate specificity between CYP2C9 and CYP2C19 can be rationalized in terms of single amino acid residue changes within the putative active site region, of which I99H appears to be the most significant.
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