Guanylate cyclase soluble subunit alpha-1 and beta-1 (sGCα1β1 or sGC (soluble guanylate cyclase; the heterodimer is most commonly designated as sGCα1β1))

Guanylate cyclase soluble subunit alpha-1 and beta-1 form the canonical soluble guanylate cyclase (sGC) heterodimer enzyme, which is the principal intracellular receptor for nitric oxide in human cells. Upon binding NO to the heme moiety within the beta-1 subunit, the enzyme undergoes a conformational change, activating its catalytic function to convert GTP to cGMP. cGMP then initiates signaling cascades leading to smooth muscle relaxation (vasodilation), inhibition of platelet aggregation, and other physiological effects crucial for cardiovascular and neural health. Dysfunction or oxidation of sGC impairs NO signaling and is implicated in hypertension, heart failure, pulmonary hypertension, and other pathologies. Both pharmacological stimulation and activation of sGC are important therapeutic strategies, with several drugs (riociguat, cinaciguat, YC-1) targeting the enzyme to restore or enhance NO/cGMP signaling, especially when NO bioavailability or sGC function is compromised. The sGC heterodimer is expressed broadly, with high levels in vascular tissue, lung, brain, and kidney.

Other names

Soluble guanylate cyclase α1β1sGC α1β1NO-sensitive guanylate cyclaseGUCY1A1 (alpha-1; gene)GUCY1B1 (beta-1; gene)Guanylyl cyclase soluble subunit alpha-1Guanylyl cyclase soluble subunit beta-1sGCNitric oxide receptor

Stimulation/activation of sGC via direct binding (riociguat, YC-1, cinaciguat stabilize the active conformation); Activation via NO binding to the heme moiety of beta-1, increasing GTP-to-cGMP conversion; Positive allosteric modulation (as with stimulators that enhance the effect of NO); Direct replacement of oxidized/inactive enzyme (cinaciguat can activate oxidized/heme-free sGC)