Protein-protein interactions of cytochromes P450 3A4 and 3A5 with their intermediate redox partners cytochromes

   


1. Orechovich Institute of Biomedical Chemistry of RAMS
2. Orechovich Institute of Biomedical Chemistry of RAMS; Engelhardt Institute of Molecular Biology of RAS
3. Institute of Bioorganic Chemistry of NAS
Type:
DOI: 10.18097/pbmc20146001017      UDK: 577.152.3      PubMed Id: 24749245
Year: 2014 vol: 60  issue:1  pages: 17-27
Abstract: Molecular interactions between proteins redox partners (cytochromes Р450 3А4, 3А5 and cytochrome b ) within the monooxygenase system, which is known to be involved in drug biotransformation, were investigated. Human cytochromes Р450 3А4 and 3А5 (CYP3A4 and CYP3A5) form complexes with various cytochromes b : 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 b mc was shown to be capable of stimulating the electrocatalytic activity of CYP3A4 to testosterone.
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Reference: Gnedenko O.V., Ivanov A.S., Yablokov E.O., Usanov S.A., Mukha D.V., Sergeev G.V., Kuzikov A.V., Bulko T.V., Moskaleva N.E., Shumyantseva V.V., Archakov A.I., Protein-protein interactions of cytochromes P450 3A4 and 3A5 with their intermediate redox partners cytochromes, Biomeditsinskaya khimiya, 2014, vol: 60(1), 17-27.
This paper is also available as the English translation:10.1134/S1990750814030068
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