Specificity of Isatin Interaction with Cytochromes P450


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Abstract

Cytochrome P450-dependent monooxygenase systems exist basically in all living organisms, where they perform various important functions. The coordinated functioning of these systems involves many proteins participating in different protein-protein interactions (PPI). Previously, we have found that the endogenous non-peptide bioregulator isatin (indoledione-2,3), synthesized from indole by means of certain cytochromes P450 (e.g. P450 2E1, P450 2C19, P450 2A6) regulates affinity of some PPI. In this study, an attempt has been undertaken to register a direct interaction of isatin with a set of different proteins related to the functioning of cytochrome P450-dependent monooxygenase systems: five isoforms of cytochromes P450, two isoforms of cytochrome b5, cytochrome P450 reductase, adrenodoxin, adrenodoxin reductase and ferrochelatase. The study has shown high affinity specific binding of isatin only to cytochromes P450 (the equilibrium dissociation constant (Kd) is about 10–8 M).

About the authors

P. V. Ershov

Institute of Biomedical Chemistry

Author for correspondence.
Email: pavel79@inbox.ru
Russian Federation, Pogodinskaya ul. 10, Moscow, 119121

Yu. V. Mezentsev

Institute of Biomedical Chemistry

Email: pavel79@inbox.ru
Russian Federation, Pogodinskaya ul. 10, Moscow, 119121

E. O. Yablokov

Institute of Biomedical Chemistry

Email: pavel79@inbox.ru
Russian Federation, Pogodinskaya ul. 10, Moscow, 119121

L. A. Kaluzhskiy

Institute of Biomedical Chemistry

Email: pavel79@inbox.ru
Russian Federation, Pogodinskaya ul. 10, Moscow, 119121

A. V. Florinskaya

Institute of Biomedical Chemistry

Email: pavel79@inbox.ru
Russian Federation, Pogodinskaya ul. 10, Moscow, 119121

A. V. Svirid

Institute of Bioorganic Chemistry

Email: pavel79@inbox.ru
Belarus, ul. Akad. Kuprevicha 5/2, Minsk, 220141

A. A. Gilep

Institute of Bioorganic Chemistry

Email: pavel79@inbox.ru
Belarus, ul. Akad. Kuprevicha 5/2, Minsk, 220141

S. A. Usanov

Institute of Bioorganic Chemistry

Email: pavel79@inbox.ru
Belarus, ul. Akad. Kuprevicha 5/2, Minsk, 220141

A. E. Medvedev

Institute of Biomedical Chemistry

Email: pavel79@inbox.ru
Russian Federation, Pogodinskaya ul. 10, Moscow, 119121

A. S. Ivanov

Institute of Biomedical Chemistry

Email: pavel79@inbox.ru
Russian Federation, Pogodinskaya ul. 10, Moscow, 119121

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