Jonathan Winger - Nitric oxide signaling: no longer simply on or off

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  TRENDS IN BIOCHEMICAL SCIENCES Volume: 31 Issue: 4 Pages: 231-239   Published: APR 2006


  Nitric oxide (NO) triggers various physiological responses in   numerous tissues by binding and activating soluble guanylate   cyclase (sGC) to produce the second messenger cGMP. In vivo,   basal NO/cGMP signaling maintains a resting state in target cells   (for example, resting tone in smooth muscle), but an acute burst   of NO/cGMP signaling triggers rapid responses (such as smooth   muscle relaxation). Recent studies have shown that the sGC   heterodimer comprises at least four modular domains per subunit.   The N-terminal heme domain is a member of the H-NOX family of   domains that bind O-2 and/or NO and are conserved in prokaryotes   and higher eukaryotes. Studies of these domains have uncovered   the molecular basis for ligand discrimination by sGC. Other work   has identified two temporally distinct states of sGC activation   by NO: formation of a stable NO-heme complex results in a   low-activity species, and additional NO produces a transient   fully active enzyme. Nucleotides also allosterically modulate the   duration and intensity of enzyme activity. Together, these   studies suggest a biochemical basis for the two distinct types of   NO/cGMP signal observed in vivo.

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