Homology modelling of human CYP2 family enzymes based on the CYP2C5 crystal structure

• Published in: Xenobiotica 2002, Vol.32 (4), p.305-323
• Main Author: Lewis, D. F. V.
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Analytical, structural and metabolic biochemistry; Aryl Hydrocarbon Hydroxylases; Biological and medical sciences; Crystallography, X-Ray; Cytochrome P-450 CYP2A6; Cytochrome P-450 CYP2B6; Cytochrome P-450 CYP2C19; Cytochrome P-450 CYP2C8; Cytochrome P-450 CYP2C9; Cytochrome P-450 CYP2D6 - chemistry; Cytochrome P-450 CYP2E1 - chemistry; Cytochrome P-450 Enzyme System - chemistry; Cytochrome P450 Family 2; Enzymes and enzyme inhibitors; Fundamental and applied biological sciences. Psychology; Humans; Mixed Function Oxygenases - chemistry; Models, Molecular; Molecular Sequence Data; Oxidoreductases; Oxidoreductases, N-Demethylating - chemistry; Protein Structure, Tertiary; Sequence Homology, Amino Acid; Steroid 16-alpha-Hydroxylase; Steroid 21-Hydroxylase - chemistry; Steroid Hydroxylases - chemistry
• ISSN: 0049-8254; 1366-5928
• DOI: 10.1080/00498250110112015

1. The construction of molecular models for human cytochromes P450 from the CYP2 family are reported, utilizing the recently available crystal structure of CYP2C5, which is also a mammalian (rabbit) form of the enzyme. 2. In particular, selective substrate interactions with CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6 and CYP2E1 are described in the context of favourable contacts with active site amino acid residues that appear to orientate each substrate for metabolism at the experimentally observed position. 3. The results are consistent with reported findings from site-directed mutagenesis experiments with the CYP2 family, and with published information on substrate metabolism.