Molecular modelling of mammalian CYP2B isoforms and their interaction with substrates, inhibitors and redox partners

摘要: 1. The construction of three-dimensional models CYP2B isozymes from rat (CYP2B1), rabbit (CYP2B4) and man (CYP2B6), based on a multiple sequence alignment with CYP102, unique eukaryotic-like bacterial P450 (in terms possessing an NADPH-dependent FAD- FMN-containing oxidoreductase redox partner) known crystal structure, is reported. 2. enzyme described are shown to be consistent experimental evidence site-directed mutagenesis studies, antibody recognition sites amino acid residues identified as being associated partner interactions, together the location key serine residue (Ser-128) likely involved in protein kinaseA-mediated phosphorylation. 3. A substantial number substrates inhibitors fit putative active agreement their reported position metabolism or mode inhibition respectively. In particular, there complementarity between characteristic non-planar geometries groups enzymes' sites. 4. Molecular modelling appears rationalize findings quantitative structure-activity relationship investigations series inhibitors.