UC Berkeley

Soluble guanylate cyclase (sGC) is responsible for transducing the gaseous signaling molecule nitric oxide (NO) into the ubiquitous secondary signaling messenger cyclic guanosine monophosphate in eukaryotic organisms. sGC is exquisitely tuned to respond to low levels of NO, allowing cells to respond to non-toxic levels of NO. In this review, the structure of sGC is discussed in the context of sGC activation and deactivation. The sequence of events in the activation pathway are described into a comprehensive model of in vivo sGC activation as elucidated both from studies with purified enzyme and those done in cells. This model is then used to discuss the deactivation of sGC, as well as the molecular mechanisms of pathophysiological deactivation.