Letter abstract
Nature Chemical Biology 1, 154 - 158 (2005)
Published online: 10 July 2005 | doi:10.1038/nchembio720
Thioredoxin catalyzes the S-nitrosation of the caspase-3 active site cysteine
Douglas A Mitchell1 & Michael A Marletta1,2,3
Nitric oxide (NO) signaling through the formation of cGMP is well established; however, there seems to be an increasing role for cGMP-independent NO signaling. Although key molecular details remain unanswered, S-nitrosation represents an example of cGMP-independent NO signaling. This modification has garnered recent attention as it has been shown to modulate the function of several important biochemical pathways1, 2, 3. Although an analogy to O-phosphorylation can be drawn4, little is known about protein nitrosothiol regulation in vivo. In solution, NO readily reacts with oxygen to yield a nitrosating agent, but this process alone provides no specificity for nitrosation5. This lack of specificity is exemplified by the in vitro poly-S-nitrosation of caspase-3 (Casp-3, ref. 6) and the ryanodine receptor7. Previous in vivo work with Casp-3 suggests that a protein-assisted process may be responsible for selective S-nitrosation of the catalytic cysteine (Cys163)8. We demonstrated that a single cysteine in thioredoxin (Trx) is capable of a targeted, reversible transnitrosation reaction with Cys163 of Casp-3. A greater understanding of how S-nitrosation is mediated has broad implications for cGMP-independent signaling. The example described here also suggests a new role for Trx in the regulation of apoptosis.
- Department of Chemistry, 211 Lewis Hall, University of California Berkeley, Berkeley, California 94720-1460, USA.
- Department of Molecular and Cell Biology, University of California Berkeley, Berkeley, California 94720-1460, USA.
- Division of Physical Biosciences, Lawrence Berkeley National Laboratory, University of California Berkeley, Berkeley, California 94720-1460, USA.
Correspondence to: Michael A Marletta1,2,3 e-mail: marletta@berkeley.edu
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