title: Molecular modelling of the mouse cytochrome P450 CYP2F2 based on the CYP102 crystal structure template and selective CYP2F2 substrate interactions.
abstract: The results of homology modelling of the mouse cytochrome P450, CYP2F2, are reported, based on the CYP102 crystallographic template. It is found that selective CYP2F2 substrates are able to fit the putative active site of the enzyme via aromatic pi-pi stacking and, in some cases, hydrogen-bonded interactions. Two alkylnaphthalenes were investigated via the model to evaluate whether they are likely to act as CYP2F2 substrates and, of these, 2-isopropyl-naphthalene was found to fit the putative active site, whereas 2-(2-hexadecyl)naphthalene was unable to do this, due to its bulky side-chain. Consequently, it is possible to utilize homology modelling to evaluate the likelihood of enzyme-substrate selectivity for CYP2F2 and predict routes of metabolism mediated by this enzyme. This procedure can therefore be used to investigate the potential for activation of xenobiotics via this enzyme, especially those related to known CYP2F substrates, such as naphthalene.
authors.affiliation: School of Biomedical and Life Sciences, University of Surrey, Guildford, Surrey, UK. d.lewis@surrey.ac.uk
authors.forename: David F V
authors.initials: DF
authors.lastname: Lewis
authors.forename: Paul T
authors.initials: PT
authors.lastname: Bailey
authors.forename: Lawrence K
authors.initials: LK
authors.lastname: Low
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000737:chemistry* / Q000235:genetics; D003460:Crystallization; D003577:Cytochrome P-450 Enzyme System / Q000737:chemistry* / Q000235:genetics; D051379:Mice; D006899:Mixed Function Oxygenases / Q000737:chemistry* / Q000235:genetics; D008958:Models, Molecular; D009251:NADPH-Ferrihemoprotein Reductase; D009281:Naphthalenes / Q000378:metabolism; D016415:Sequence Alignment; D017421:Sequence Analysis; D017386:Sequence Homology, Amino Acid; D012862:Skatole / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D009281:Naphthalenes; C031721:naphthalene; D003577:Cytochrome P-450 Enzyme System; D012862:Skatole; D006899:Mixed Function Oxygenases; C110333:Cyp2f2 protein, mouse; D009251:NADPH-Ferrihemoprotein Reductase; C052423:flavocytochrome P450 BM3 monoxygenases