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

Gnedenko O.V.1 , Ivanov A.S.1, Yablokov E.O.2, Usanov S.A.3, Mukha D.V.3, Sergeev G.V.3, Kuzikov A.V.1, Bulko T.V.1, Moskaleva N.E.1, Shumyantseva V.V.1, Archakov A.I.1

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
DOI: 10.18097/PBMC20146001017      PubMed Id: 24749245
Year: 2014  Volume: 60  Issue: 1  Pages: 17-27
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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Keywords: SPR biosensor, protein-protein interactions, cytochromes P450, cytochrome b, electrochemistry, electrocatalysis, electron transfer

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. (2014). Protein-protein interactions of cytochromes P450 3A4 and 3A5 with their intermediate redox partners cytochromes. Biomeditsinskaya Khimiya, 60(1), 17-27.
This paper is also available as the English translation: 10.1134/S1990750814030068
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