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Enzymatic mechanisms regulating protein S-nitrosylation: implications in health and disease

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Abstract

Nitric oxide participates in cellular signal transduction largely through S-nitrosylation of allosteric and active-site cysteine thiols within proteins, forming S-nitroso-proteins (SNO-proteins). S-nitrosylation of proteins has been demonstrated to affect a broad range of functional parameters including enzymatic activity, subcellular localization, protein–protein interactions, and protein stability. Analogous to other ubiquitous posttranslational modifications that are regulated enzymatically, including phosphorylation and ubiquitinylation, accumulating evidence suggests the existence of enzymatic mechanisms for regulating protein S-nitrosylation. In particular, studies have led to the identification of multiple enzymes (nitrosylases and denitrosylases) that participate in targeted S-nitrosylation or denitrosylation of proteins in physiological settings. Nitrosylases are best characterized in the context of transnitrosylation in which a SNO-protein transfers an NO group to an acceptor protein (Cys-to-Cys transfer), but examples of transnitrosylation catalyzed by metalloproteins (Metal-to-Cys transfer) also exist. By contrast, denitrosylases remove the NO group from SNO-proteins, ultimately using reducing equivalents derived from NADH or NADPH. Here, we focus on the recent discoveries of nitrosylases and denitrosylases and the notion that their aberrant activities may play roles in health and disease.

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Acknowledgements

This work was supported by National Institutes of Health Grants R01HL059130, R01HL095463, R01HL091876, and P01HL75443 and by DARPA N66001-10-C-2015. The authors thank Dr. Douglas T. Hess for the discussion and advice.

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Authors and Affiliations

  1. Institute for Transformative Molecular Medicine and Department of Medicine, Case Western Reserve University and University Hospitals Case Medical Center, Cleveland, OH, 44106, USA

    Puneet Anand & Jonathan S. Stamler

  2. Graduate Training Program, Department of Biochemistry, Duke University Medical Center, Durham, NC, 27710, USA

    Puneet Anand

  3. Institute for Transformative Molecular Medicine, Wolstein Research Building 5522, 2103 Cornell Road, Cleveland, OH, 44106, USA

    Jonathan S. Stamler

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  1. Puneet Anand
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Correspondence to Jonathan S. Stamler.

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Anand, P., Stamler, J.S. Enzymatic mechanisms regulating protein S-nitrosylation: implications in health and disease. J Mol Med 90, 233–244 (2012). https://doi.org/10.1007/s00109-012-0878-z

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  • DOI: https://doi.org/10.1007/s00109-012-0878-z

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