Moonlighting Biochemistry of Cysteine Synthase: A Species-specific Global Regulator

Singh, Ravi P. and Saini, Neha and Sharma, Gaurav and Rahisuddin, R. and Patel, Madhuri and Kaushik, Abhishek and Kumaran, S. (2021) Moonlighting Biochemistry of Cysteine Synthase: A Species-specific Global Regulator. Journal of molecular biology, 433 (5). ISSN 0022-2836

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Abstract

Cysteine Synthase (CS), the enzyme that synthesizes cysteine, performs non-canonical regulatory roles by binding and modulating functions of disparate proteins. Beyond its role in catalysis and regulation in the cysteine biosynthesis pathway, it exerts its moonlighting effect by binding to few other proteins which possess a C-terminal "CS-binding motif", ending with a terminal ILE. Therefore, we hypothesized that CS might regulate many other disparate proteins with the "CS-binding motif". In this study, we developed an iterative sequence matching method for mapping moonlighting biochemistry of CS and validated our prediction by analytical and structural approaches. Using a minimal protein-peptide interaction system, we show that five previously unknown CS-binder proteins that participate in diverse metabolic processes interact with CS in a species-specific manner. Furthermore, results show that signatures of protein-protein interactions, including thermodynamic, competitive-inhibition, and structural features, highly match the known CS-Binder, serine acetyltransferase (SAT). Together, the results presented in this study allow us to map the extreme multifunctional space (EMS) of CS and reveal the biochemistry of moonlighting space, a subset of EMS. We believe that the integrated computational and experimental workflow developed here could be further modified and extended to study protein-specific moonlighting properties of multifunctional proteins.

Item Type: Article
Additional Information: The Copyright of this article belongs to ELSEVIER
Uncontrolled Keywords: Bioinformatics; cysteine synthase; moonlighting proteins; protein structures; protein–peptide interactions
Subjects: Q Science > QR Microbiology
Depositing User: Dr. K.P.S.Sengar
Date Deposited: 19 Apr 2022 06:17
Last Modified: 19 Apr 2022 06:17
URI: http://crdd.osdd.net/open/id/eprint/2959

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