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Sci. Signal., 10 November 2009
Vol. 2, Issue 96, p. ra72
[DOI: 10.1126/scisignal.2000464]


H2S Signals Through Protein S-Sulfhydration

Asif K. Mustafa1, Moataz M. Gadalla2, Nilkantha Sen1, Seyun Kim1, Weitong Mu1, Sadia K. Gazi1, Roxanne K. Barrow1, Guangdong Yang3, Rui Wang3, and Solomon H. Snyder1,2,4*

1 Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
2 Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
3 Department of Biology, Lakehead University, Thunder Bay, Ontario, Canada P7B 5E1.
4 Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.

Abstract: Hydrogen sulfide (H2S), a messenger molecule generated by cystathionine {gamma}-lyase, acts as a physiologic vasorelaxant. Mechanisms whereby H2S signals have been elusive. We now show that H2S physiologically modifies cysteines in a large number of proteins by S-sulfhydration. About 10 to 25% of many liver proteins, including actin, tubulin, and glyceraldehyde-3-phosphate dehydrogenase (GAPDH), are sulfhydrated under physiological conditions. Sulfhydration augments GAPDH activity and enhances actin polymerization. Sulfhydration thus appears to be a physiologic posttranslational modification for proteins.

* To whom correspondence should be addressed. E-mail: ssnyder{at}

Citation: A. K. Mustafa, M. M. Gadalla, N. Sen, S. Kim, W. Mu, S. K. Gazi, R. K. Barrow, G. Yang, R. Wang, S. H. Snyder, H2S Signals Through Protein S-Sulfhydration. Sci. Signal. 2, ra72 (2009).

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