Molecular modelling of CYP4A subfamily members based on sequence homology with CYP102.
1. Homology modelling of various members of the CYP4A subfamily based on the CYP102 template structure is reported. 2. The binding interactions of specific substrates to the CYP4A forms from rat (CYP4A1), human (CYP4A11) and rabbit (CYP4A4) are shown to be consistent with experimental evidence regarding regioselectivity of metabolism. 3. The differences in substrate specificity between CYP4A1, CYP4A11 and CYP4A4 towards fatty acids and prostaglandins respectively are rationalized in terms of variations in active site amino residues.
Lewis
D F
DF
Molecular Toxicology Group, School of Biological Sciences, University of Surrey, UK. d.lewis@surrey.ac.uk
Lake
B G
BG
D000818:Animals; D001426:Bacterial Proteins; D001665:Binding Sites; D042926:Cytochrome P-450 CYP4A; D003577:Cytochrome P-450 Enzyme System / Q000737:chemistry* / Q000378:metabolism; D005227:Fatty Acids / Q000378:metabolism; D006801:Humans; D006899:Mixed Function Oxygenases / Q000737:chemistry* / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009251:NADPH-Ferrihemoprotein Reductase; D011487:Protein Conformation; D011817:Rabbits; D051381:Rats; D017386:Sequence Homology, Amino Acid; D013379:Substrate Specificity
D001426:Bacterial Proteins; D005227:Fatty Acids; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D042926:Cytochrome P-450 CYP4A; D009251:NADPH-Ferrihemoprotein Reductase; C052423:flavocytochrome P450 BM3 monoxygenases