Soluble guanylate cyclase alpha-1 beta-1 (sGC α1β1)

Soluble guanylate cyclase (sGC) is a heterodimeric enzyme, most commonly composed of α1 and β1 subunits, that serves as the primary intracellular receptor for nitric oxide (NO) (UniProt: P14314, Q02108). Upon binding NO to its prosthetic heme group, sGC catalyzes the conversion of guanosine triphosphate (GTP) into cyclic guanosine monophosphate (cGMP), a potent second messenger (PubMed: 28103460). This signaling cascade mediates critical physiological processes, including vascular smooth muscle relaxation, inhibition of platelet activation, and modulation of cardiac contractility (StatPearls: NBK542200). Dysregulation of the NO-sGC-cGMP pathway is a hallmark of various cardiovascular and fibrotic diseases, often characterized by reduced NO bioavailability or oxidative damage to the sGC heme group (PubMed: 30249010). Therapeutic agents such as sGC stimulators (e.g., riociguat, vericiguat) and activators have been developed to bypass these impairments, promoting cGMP production to treat conditions like pulmonary arterial hypertension and chronic heart failure (PubChem: CID 11960521). These drugs work by either sensitizing the enzyme to available NO or directly activating the enzyme in its oxidized, heme-free state, thereby restoring essential signaling in diseased tissues (PubMed: 25034015).

Other names

sGCGuanylate cyclase 1 soluble subunit alpha 3Guanylate cyclase 1 soluble subunit beta 3GUCY1A3/GUCY1B3NO-sensitive guanylyl cyclase

Soluble guanylate cyclase stimulators increase the sensitivity of the enzyme to nitric oxide and directly stimulate the enzyme at a site distinct from the nitric oxide binding site, while activators target the oxidized or heme-free form of the enzyme to restore cGMP production.