Guanylate cyclase and the (NO)-N-./cGMP signaling pathway

Signal transduction with the diatomic radical nitric oxide (NO) is involved in a number of important physiological processes, including smooth muscle relaxation and neurotransmission. Soluble guanylate cyclase (sGC), a hetero dimeric enzyme that converts guanosine triphosphate to cyclic guanosine mon ophosphate, is a critical component of this signaling pathway, sGC is a hem oprotein; it is through the specific interaction of NO with the sGC heme th at sGC is activated. Over the last decade, much has been learned about the unique heme environment of sGC and its interaction with ligands like NO and carbon monoxide. This review will focus on the role of sGC in signaling, i ts relationship to the other nucleotide cyclases, and on what is known abou t sGC genetics, heme environment and catalysis. The latest understanding in regard to sGC will be incorporated to build a model of sGC structure, acti vation, catalytic mechanism and deactivation. (C) 1999 Elsevier Science B.V . All rights reserved.