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
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. et al. Protein-protein interactions of cytochromes P450 3A4 and 3A5 with their intermediate redox partners cytochromes // Biomeditsinskaya Khimiya. - 2014. - V. 60. -N 1. - P. 17-27.
Gnedenko O.V. et al., "Protein-protein interactions of cytochromes P450 3A4 and 3A5 with their intermediate redox partners cytochromes." Biomeditsinskaya Khimiya 60.1 (2014): 17-27.
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.
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