Insights into multifaceted activities of CysK for therapeutic interventions

Abstract

CysK (O-acetylserine sulfhydrylase) is a pyridoxal-5′ phosphate-dependent enzyme which catalyzes the second step of the de novo cysteine biosynthesis pathway by converting O-acetyl serine (OAS) into l-cysteine in the presence of sulfide. The first step of the cysteine biosynthesis involves formation of OAS from serine and acetyl CoA by CysE (serine acetyltransferase). Apart from role of CysK in cysteine biosynthesis, recent studies have revealed various additional roles of this enzyme in bacterial physiology. Other than the suggested regulatory role in cysteine production, other activities of CysK include involvement of CysK-in contact-dependent toxin activation in Gram-negative pathogens, as a transcriptional regulator of CymR by stabilizing the CymR-DNA interactions, in biofilm formation by providing cysteine and via another mechanism not yet understood, in ofloxacin and tellurite resistance as well as in cysteine desulfurization. Some of these activities involve binding of CysK to another cellular partner, where the complex is regulated by the availability of OAS and/or sulfide (H2S). The aim of this study is to present an overview of current knowledge of multiple functions performed by CysK and identifying structural features involved in alternate functions. Due to possible role in disease, promoting or inhibiting a “moonlighting” function of CysK could be a target for developing novel therapeutic interventions.

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Acknowledgements

Authors are grateful to Indian Council for Medical Research (ICMR), Government of India, for the research grant (BIC/12(16)/2012). We sincerely thank Department of Biotechnology, Jaypee Institute of Information Technology for providing an opportunity to present this work at International Conference on Advances in Biosciences and Biotechnology—2018.

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Joshi, P., Gupta, A. & Gupta, V. Insights into multifaceted activities of CysK for therapeutic interventions. 3 Biotech 9, 44 (2019). https://doi.org/10.1007/s13205-019-1572-4

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Keywords

  • CysK
  • Cysteine biosynthesis pathway
  • Cysteine synthase complex
  • Multifaceted roles
  • Contact-dependent growth inhibition
  • Ofloxacin resistance
  • Tellurite resistance
  • CymR regulation
  • Biofilm formation
  • Cysteine desulfurization
  • CysK inhibitors
  • Moonlighting functions