Guanylate cyclase and the .NO/cGMP signaling pathway

Biochim Biophys Acta. 1999 May 5;1411(2-3):334-50. doi: 10.1016/s0005-2728(99)00024-9.


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 heterodimeric enzyme that converts guanosine triphosphate to cyclic guanosine monophosphate, is a critical component of this signaling pathway. sGC is a hemoprotein; it is through the specific interaction of NO with the sGC heme that 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, its relationship to the other nucleotide cyclases, and on what is known about sGC genetics, heme environment and catalysis. The latest understanding in regard to sGC will be incorporated to build a model of sGC structure, activation, catalytic mechanism and deactivation.

Publication types

  • Review

MeSH terms

  • Animals
  • Catalysis
  • Cell Line
  • Cyclic GMP / chemistry*
  • Cyclic GMP / metabolism
  • Enzyme Activation
  • Free Radicals / chemistry
  • Gene Expression
  • Guanylate Cyclase / chemistry*
  • Guanylate Cyclase / genetics
  • Guanylate Cyclase / metabolism
  • Humans
  • Models, Chemical
  • Nitric Oxide / chemistry*
  • Nitric Oxide / metabolism
  • Nitric Oxide Synthase / chemistry
  • Signal Transduction
  • Structure-Activity Relationship


  • Free Radicals
  • Nitric Oxide
  • Nitric Oxide Synthase
  • Guanylate Cyclase
  • Cyclic GMP