title: Exhaustive computational search of ionic-charge clusters that mediate interactions between mammalian cytochrome P450 (CYP) and P450-oxidoreductase (POR) proteins.
abstract: In this work, a model for the interaction between CYP2B4 and the FMN domain of rat P450-oxidoreductase is built using as template the structure of a bacterial redox complex. Amino acid residues identified in the literature as cytochrome P450 (CYP)-redox partner interfacial residues map to the interface in our model. Our model supports the view that the bacterial template represents a specific electron transfer complex and moreover provides a structural framework for explaining previous experimental data. We have used our model in an exhaustive search for complementary pairs of mammalian CYP and P450-oxidoreductase (POR) charge clusters. We quantitatively show that among the previously defined basic clusters, the 433K-434R cluster is the most dominant (32.3% of interactions) and among the acidic clusters, the 207D-208D-209D cluster is the most dominant (29%). Our analysis also reveals the previously not described basic cluster 343R-345K (16.1% of interactions) and 373K (3.2%) and the acidic clusters 113D-115E-116E (25.8%), 92E-93E (12.9%), 101D (3.2%) and 179E (3.2%). Cluster pairings among the previously defined charge clusters include the pairing of cluster 421K-422R to cluster 207D-208D-209D. Moreover, 433K-434R and 207D-208D-209D, respectively the dominant positively and negatively charged clusters, are uncorrelated. Instead our analysis suggests that the newly identified cluster 113D-115E-116E is the main partner of the 433K-434R cluster while the newly described cluster 343R-345K is correlated to the cluster 207D-208D-209D.
authors: Division of Medical Biochemistry, Institute for Infectious Disease & Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Observatory 7925, South Africa. Alexander.Zawaira@uct.ac.za
authors: Alexander
authors: A
authors: Zawaira
authors: Marco
authors: M
authors: Gallotta
authors: Natasha
authors: N
authors: Beeton-Kempen
authors: Lauren
authors: L
authors: Coulson
authors: Patrick
authors: P
authors: Marais
authors: Michelle
authors: M
authors: Kuttel
authors: Jonathan
authors: J
authors: Blackburn
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D003198:Computer Simulation; D003577:Cytochrome P-450 Enzyme System / Q000737:chemistry* / Q000378:metabolism*; D009251:NADPH-Ferrihemoprotein Reductase / Q000737:chemistry* / Q000378:metabolism*; D010084:Oxidation-Reduction; D011485:Protein Binding; D011487:Protein Conformation; D051381:Rats; D016415:Sequence Alignment; D020539:Sequence Analysis, Protein; D055672:Static Electricity
chemical_list: D003577:Cytochrome P-450 Enzyme System; D009251:NADPH-Ferrihemoprotein Reductase