S-nitrosylation: spectrum and specificity

DT Hess, A Matsumoto, R Nudelman, JS Stamler - Nature cell biology, 2001 - nature.com
DT Hess, A Matsumoto, R Nudelman, JS Stamler
Nature cell biology, 2001nature.com
The award of the 1998 Nobel Prize in Physiology was based upon the earlier and seminal
demonstration that nitric oxide (NO) generated by endothelial cells relaxes vascular smooth
muscle through activation of guanylate cyclase. These findings provided a preliminary
perspective from which NO could be viewed as a freelydiffusible second messenger with a
promiscuous sphere of influence, that acts largely through regulation of cyclic GMP (cGMP)
production. However, this view has been altered fundamentally by a spate of findings …
The award of the 1998 Nobel Prize in Physiology was based upon the earlier and seminal demonstration that nitric oxide (NO) generated by endothelial cells relaxes vascular smooth muscle through activation of guanylate cyclase. These findings provided a preliminary perspective from which NO could be viewed as a freelydiffusible second messenger with a promiscuous sphere of influence, that acts largely through regulation of cyclic GMP (cGMP) production. However, this view has been altered fundamentally by a spate of findings indicating that NO may target cysteine thiols and transition-metal centres of proteins with exquisite spatial and temporal resolution, and that these modifications may modulate protein function to transduce a panoply of cGMP-independent cellularcontrol signals. This accumulating evidence indicates that the covalent attachment of NO groups to protein sulphydryls and transition metals is an example of a preciselyregulated post-translational protein modification1, 2.
A significant impediment to the detailed analysis of regulation by NO of protein function has been the technical difficulty of identifying and isolating endogenously modified substrates, to characterize physiologically induced turnover of the NO moiety in situ. Indeed, although functional regulation by NO has been described for several disparate proteins in their native environment (including haemoglobin3, the ryanodine receptor–Ca2+ channel4, the N-methyl-D-aspartate (NMDA) receptor-coupled ion channel5, methionine adenosyltransferase6 and the apoptotic protease caspase-3 (ref. 7)), most studies of proteins that have been identified as substrates for S-nitrosylation (almost 100 so far) used greatly simplified in vitro preparations and/or relied on exogenous NO donors rather than NO produced physiologically by endogenous enzymes.
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