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Article

Mechanism of the Affinity-Enhancing Effect of Isatin on Human Ferrochelatase and Adrenodoxin Reductase Complex Formation: Implication for Protein Interactome Regulation

1
Institute of Biomedical Chemistry, 10 Building 8, Pogodinskaya Street, 140006 Moscow, Russia
2
Institute of Bioorganic Chemistry NASB, 5 Building 2, V.F. Kuprevich Street, 220141 Minsk, Belarus
3
Far East Federal University, FEFU Campus, 10 Ajax Bay, Russky Island, 690922 Vladivostok, Russia
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(20), 7605; https://doi.org/10.3390/ijms21207605
Received: 21 September 2020 / Revised: 9 October 2020 / Accepted: 12 October 2020 / Published: 14 October 2020
Isatin (indole-2, 3-dione) is a non-peptide endogenous bioregulator exhibiting a wide spectrum of biological activity, realized in the cell via interactions with numerous isatin-binding proteins, their complexes, and (sub) interactomes. There is increasing evidence that isatin may be involved in the regulation of complex formations by modulating the affinity of the interacting protein partners. Recently, using Surface Plasmon Resonance (SPR) analysis, we have found that isatin in a concentration dependent manner increased interaction between two human mitochondrial proteins, ferrochelatase (FECH), and adrenodoxine reductase (ADR). In this study, we have investigated the affinity-enhancing effect of isatin on the FECH/ADR interaction. The SPR analysis has shown that FECH forms not only homodimers, but also FECH/ADR heterodimers. The affinity-enhancing effect of isatin on the FECH/ADR interaction was highly specific and was not reproduced by structural analogues of isatin. Bioinformatic analysis performed using three dimensional (3D) models of the interacting proteins and in silico molecular docking revealed the most probable mechanism involving FECH/isatin/ADR ternary complex formation. In this complex, isatin is targeted to the interface of interacting FECH and ADR monomers, forming hydrogen bonds with both FECH and ADR. This is a new regulatory mechanism by which isatin can modulate protein–protein interactions (PPI). View Full-Text
Keywords: ferrochelatase; adrenodoxin reductase; isatin; in silico; affinity; complex formation; heterodimerization; surface plasmon resonance ferrochelatase; adrenodoxin reductase; isatin; in silico; affinity; complex formation; heterodimerization; surface plasmon resonance
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MDPI and ACS Style

Ershov, P.V.; Veselovsky, A.V.; Mezentsev, Y.V.; Yablokov, E.O.; Kaluzhskiy, L.A.; Tumilovich, A.M.; Kavaleuski, A.A.; Gilep, A.A.; Moskovkina, T.V.; Medvedev, A.E.; Ivanov, A.S. Mechanism of the Affinity-Enhancing Effect of Isatin on Human Ferrochelatase and Adrenodoxin Reductase Complex Formation: Implication for Protein Interactome Regulation. Int. J. Mol. Sci. 2020, 21, 7605. https://doi.org/10.3390/ijms21207605

AMA Style

Ershov PV, Veselovsky AV, Mezentsev YV, Yablokov EO, Kaluzhskiy LA, Tumilovich AM, Kavaleuski AA, Gilep AA, Moskovkina TV, Medvedev AE, Ivanov AS. Mechanism of the Affinity-Enhancing Effect of Isatin on Human Ferrochelatase and Adrenodoxin Reductase Complex Formation: Implication for Protein Interactome Regulation. International Journal of Molecular Sciences. 2020; 21(20):7605. https://doi.org/10.3390/ijms21207605

Chicago/Turabian Style

Ershov, Pavel V., Alexander V. Veselovsky, Yuri V. Mezentsev, Evgeniy O. Yablokov, Leonid A. Kaluzhskiy, Anastasiya M. Tumilovich, Anton A. Kavaleuski, Andrei A. Gilep, Taisiya V. Moskovkina, Alexei E. Medvedev, and Alexis S. Ivanov 2020. "Mechanism of the Affinity-Enhancing Effect of Isatin on Human Ferrochelatase and Adrenodoxin Reductase Complex Formation: Implication for Protein Interactome Regulation" International Journal of Molecular Sciences 21, no. 20: 7605. https://doi.org/10.3390/ijms21207605

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