Molecular modelling of CYP4A subfamily members based on sequence homology with CYP102

Authors
Lewis, DFV Lake, BG
Citation
Dfv. Lewis et Bg. Lake, Molecular modelling of CYP4A subfamily members based on sequence homology with CYP102, XENOBIOTICA, 29(8), 1999, pp. 763-781
Citations number
62
Categorie Soggetti
Pharmacology & Toxicology
Journal title
XENOBIOTICA
ISSN journal
00498254 → ACNP
Volume
29
Issue
8
Year of publication
1999
Pages
763 - 781
Database
ISI
SICI code
0049-8254(199908)29:8<763:MMOCSM>2.0.ZU;2-F
Abstract
1. Homology modelling of various members of the CYP4A subfamily based on th e 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 consisten t with experimental evidence regarding regioselectivity of metabolism. 3. The differences in substrate specificity between CYP4A1, CYP4A11 and CYP 4A4 towards fatty acids and prostaglandins respectively are rationalized in terms of variations in active site amino residues.