Molecular modelling of CYP1 family enzymes CYP1A1, CYP1A2, CYP1A6 and CYP1B1 based on sequence homology with CYP102

Molecular modelling of a number of CYP1 family enzymes from rat, plaice and human is described based on amino acid sequence homology with the haemopro tein domain of CYP102, a unique bacterial P450 of known structure. The inte raction of various substrates and inhibitors within the putative active sit es of rat CYP1A1, human CYP1A2, a fish CYP1 enzyme CYP1A6 (from plaice) and human CYP1B1, is shown to be consistent with P450-mediated oxidation in ea ch example or, in the case of inhibitors, mechanism of inhibition. It is re ported that relatively small changes between the enzymes' active site regio ns assist in the rationalization of CYP1 enzyme preferences for particular substrate types, and a template of superimposed CYP1A2 substrates is shown to fit the putative active site of the human CYP1A2 enzyme. (C) 1999 Elsevi er Science Ireland Ltd. All rights reserved.