Soluble guanylate cyclase beta-1 subunit (sGC β1)

The soluble guanylate cyclase beta-1 subunit is a heme-containing enzyme subunit that, together with an alpha subunit, forms the heterodimeric receptor for nitric oxide in mammalian cells. Upon nitric oxide binding at the heme group in its N-terminal H-NOX domain, the beta-1 subunit enables activation of the catalytic domain, which then synthesizes cyclic GMP (cGMP) from GTP. The production of cGMP is a ubiquitous signaling event central to vasodilation, cardiovascular homeostasis, platelet inhibition, and anti-inflammatory pathways. sGC β1 is validated as a key therapeutic target, especially for drugs treating cardiovascular diseases such as pulmonary hypertension and heart failure. Multiple drugs interact directly with sGC β1, either by mimicking or enhancing the effect of nitric oxide, thereby promoting beneficial vascular effects. Safety profiles of sGC-targeting therapies center on excessive vasodilation and bleeding; efficacy is commonly monitored via cGMP levels. No significant errors or confusion were found regarding the specificity or molecular identity of this target; “Soluble Guanylate Cyclase Beta 1 Subunit” is an accepted and precise designation for the β1 component of the canonical sGC heterodimer.

Other names

Guanylate cyclase soluble subunit beta-1GUCY1B3GC-1 β1sGC beta-1 subunit

**Activation by nitric oxide**: NO binds to the heme group of the β1 subunit H-NOX domain, triggering conformational changes that activate the catalysis of GTP to cGMP. **Pharmacological activation**: Drugs (e.g., riociguat, YC-1, cinaciguat) bind to and can stimulate or activate sGC either in the presence or absence of NO, increasing cGMP production. **Downstream effects**: Increased cGMP leads to vasodilation, inhibition of platelet aggregation, and anti-inflammatory effects.