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Soluble guanylate cyclase (sGC) is the primary nitric oxide (NO) sensor. It plays a central role in NO signalling and is implicated in many essential physiological processes and disease conditions. The binding of NO leads to a significant boost in sGC enzymatic activity. However, the mechanism of NO activation remains incompletely understood. Here we report the cryo-electron microscopy structures of the human sGC α1β1 heterodimer in different functional states. These structures revealed that the transducer module bridges the NO sensor module and the catalytic module. NO binding to the β1 heme-nitric oxide and oxygen binding (H-NOX) domain triggers the structural rearrangement of the sensor module and the bending-straightening conformational switch of the transducer module. The resulting movement of the N termini of the catalytic domains drives the structural changes within the catalytic module, which in turn boost sGC enzymatic activity.
This article was published in the following journal.
Signaling pathways that involve diatomic gases in photosynthetic organisms are not well understood. Exposure to nitric oxide or carbon monoxide is known to elicit certain responses in some photosynthe...
BAY 41-2272 is a guanylyl cyclase (GC) stimulator derived from YC-1 (3-[(5'-hydroxymethyl-2'-furyl)-1-benzyl indazole]). Previous studies by our group showed that BAY 41-2272 activates human monocytes...
Electronic cigarette refill liquids are commercially provided with a wide variety of flavoring agents. A recent study suggested that several common flavors may scavenge nitric oxide (NO) and cause end...
We showed previously an epinephrine-induced inhibition of the Na+/K+ ATPase in Caco-2 cells mediated via PGE2. This work is an attempt to further elucidate mediators downstream of PGE2 and involved in...
Human guanylate binding protein 1 (hGBP1) belongs to the family of dynamin-like proteins and is activated by addition of nucleotides, leading to protein oligomerization and stimulated GTPase activity....
To evaluate the effect of itraconazole (a potent cytochrome P450 isoenzyme [CYP]3A inhibitor) on the pharmacokinetics (PK) of olinciguat
The primary objective of the study is to evaluate the effect of itraconazole (a potent cytochrome P450 isoenzyme [CYP]3A inhibitor) on the pharmacokinetics of IW-1973.
To evaluate the safety and efficacy of IW-1973 in patients with type 2 diabetes mellitus with albuminuria who are on a stable regimen of renin-angiotensin system inhibitors.
The primary objective of the 1701-202 STRONG SCD study is to evaluate the safety and tolerability of 3 dose levels of IW-1701 compared with placebo when administered daily for approximatel...
The objectives of the study are to assess the safety and tolerability of a range of single doses of IW-1701 when administered as oral capsules to healthy subjects, to determine the pharmac...
A class of cellular membrane receptors that either have an intrinsic guanylate cyclase activity or are closely coupled to specific guanylate cyclases within the cell.
Neuronal calcium sensor proteins that regulate the activation of membrane-bound GUANYLATE CYCLASE. They are primarily expressed in the RETINA where they play an important role in PHOTOTRANSDUCTION.
A mammalian enzyme composed of a heterodimer of alpha and beta subunits. Each subunit consists of four domains; N-terminal HNOX domain, PAS-like domain, a coiled-coil domain, and a C-terminal catalytic domain. All four domains are homologous proteins with a similar conformation of functional domains. Soluble guanylate cyclase catalyzes the formation of cyclic GMP from GTP, and is a key enzyme of the nitric oxide signaling pathway involved in the regulation of a variety of biological and physiological processes in mammals.
A volatile vasodilator which relieves ANGINA PECTORIS by stimulating GUANYLATE CYCLASE and lowering cytosolic calcium. It is also sometimes used for TOCOLYSIS and explosives.
An enzyme that catalyzes the conversion of GTP to 3',5'-cyclic GMP and pyrophosphate. It also acts on ITP and dGTP. (From Enzyme Nomenclature, 1992) EC 184.108.40.206.