title: [Protein-protein interactions of cytochromes P450 3A4 and 3A5 with their intermediate redox partners cytochromes b5].
abstract: Molecular interactions between proteins redox partners (cytochromes P450 3A4, 3A5 and cytochrome b5) within the monooxygenase system, which is known to be involved in drug biotransformation, were investigated. Human cytochromes P450 3A4 and 3A5 (CYP3A4 and CYP3A5) form complexes with various cytochromes b5: the microsomal (b5mc) and mitochondrial (b5om) forms of this protein, as well as with 2 "chimeric" proteins, b5(om-mc), b5(mc-om). Kinetic constants and equilibrium dissociation constants were determined by the SPR biosensor. Essential distinction between CYP3A4 and CYP3A5 was only observed upon their interactions with cytochrome b5om. Electroanalytical characteristics of electrodes with immobilized hemoproteins were obtained. The electrochemical analysis of CYP3A4, CYP3A5, b5mc, b5om, b5(om-mc), and b5(mc-om) immobilized on screen printed graphite electrodes modified with membranous matrix revealed that these proteins have very close reduction potentials -0.435 - -0.350 V (vs. Ag/AgCl). Cytochrome b5mc was shown to be capable of stimulating the electrocatalytic activity of CYP3A4 to testosterone.
authors.forename: O V
authors.initials: OV
authors.lastname: Gnedenko
authors.forename: A S
authors.initials: AS
authors.lastname: Ivanov
authors.forename: E O
authors.initials: EO
authors.lastname: Iablokov
authors.forename: S A
authors.initials: SA
authors.lastname: Usanov
authors.forename: D V
authors.initials: DV
authors.lastname: Mukha
authors.forename: G V
authors.initials: GV
authors.lastname: Sergeev
authors.forename: A V
authors.initials: AV
authors.lastname: Kuzikov
authors.forename: N E
authors.initials: NE
authors.lastname: Moskaleva
authors.forename: T V
authors.initials: TV
authors.lastname: Bulko
authors.forename: V V
authors.initials: VV
authors.lastname: Shumiantseva
authors.forename: A I
authors.initials: AI
authors.lastname: Archakov
mesh_terms: D055162:Biocatalysis; D015374:Biosensing Techniques; D051544:Cytochrome P-450 CYP3A / Q000737:chemistry* / Q000235:genetics; D015786:Cytochromes b5 / Q000737:chemistry* / Q000235:genetics; D055664:Electrochemical Techniques; D004566:Electrodes; D006801:Humans; D055767:Immobilized Proteins / Q000737:chemistry / Q000235:genetics; D007700:Kinetics; D008861:Microsomes / Q000737:chemistry*; D024101:Mitochondrial Proteins / Q000737:chemistry* / Q000235:genetics; D010084:Oxidation-Reduction; D011485:Protein Binding; D011993:Recombinant Fusion Proteins / Q000737:chemistry* / Q000235:genetics; D012996:Solutions; D013739:Testosterone / Q000737:chemistry
chemical_list: D055767:Immobilized Proteins; D024101:Mitochondrial Proteins; D011993:Recombinant Fusion Proteins; D012996:Solutions; D013739:Testosterone; D015786:Cytochromes b5; C510164:CYP3A5 protein, human; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human