title: Functional interaction of cytochrome P450 with its redox partners: a critical assessment and update of the topology of predicted contact regions.
abstract: The problem of donor-acceptor recognition has been the most important and intriguing one in the area of P450 research. The present review outlines the topological background of electron-transfer complex formation, showing that the progress in collaborative investigations, combining physical techniques with chemical-modification and immunolocalization studies as well as site-directed mutagenesis experiments, has increasingly enabled the substantiation of hypothetical work resulting from homology modelling of P450s. Circumstantial analysis reveals the contact regions for redox proteins to cluster on the proximal face of P450s, constituting parts of the highly conserved, heme-binding core fold. However, more variable structural components located in the periphery of the hemoprotein molecules also participate in donor docking. The cross-reactivity of electron carriers, purified from pro- and eukaryotic sources, with a diversity of P450 species points at a possible evolutionary conservation of common anchoring domains. While electrostatic mechanisms appear to dominate orientation toward each other of the redox partners to generate pre-collisional encounter complexes, hydrophobic forces are likely to foster electron transfer events by through-bonding or pi-stacking interactions. Moreover, electron-tunneling pathways seem to be operative as well. The availability of new P450 crystal structures together with improved validation strategies will undoubtedly permit the production of increasingly satisfactory three-dimensional donor-acceptor models serving to better understand the molecular principles governing functional association of the redox proteins.
authors.affiliation: Walther-Straub-Institut für Pharmakologie und Toxikologie, Nussbaumstrasse 26, D-80336, Munich, Germany. hlavica@lrz.uni-muenchen.de
authors.forename: P
authors.initials: P
authors.lastname: Hlavica
authors.forename: J
authors.initials: J
authors.lastname: Schulze
authors.forename: D F V
authors.initials: DF
authors.lastname: Lewis
mesh_terms: D000818:Animals; D001665:Binding Sites; D003577:Cytochrome P-450 Enzyme System / Q000737:chemistry* / Q000145:classification / Q000378:metabolism / Q000502:physiology*; D004579:Electron Transport; D000939:Epitopes; D006801:Humans; D008958:Models, Molecular; D010084:Oxidation-Reduction; D011485:Protein Binding; D011487:Protein Conformation
chemical_list: D000939:Epitopes; D003577:Cytochrome P-450 Enzyme System