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Guanylate cyclase (EC 4.6.1.2, also known as guanyl cyclase, guanylyl cyclase, or GC; systematic name GTP diphosphate-lyase (cyclizing; 3′,5′-cyclic-GMP-forming)) is a lyase enzyme that converts guanosine triphosphate (GTP) to cyclic guanosine monophosphate (cGMP) and pyrophosphate: [1] GTP = 3′,5′-cyclic GMP + diphosphate
Cyclic guanosine monophosphate (cGMP) is a cyclic nucleotide derived from guanosine triphosphate (GTP). cGMP acts as a second messenger much like cyclic AMP. Its most likely mechanism of action is activation of intracellular protein kinases in response to the binding of membrane-impermeable peptide hormones to the external cell surface. [1]
Conformational change occurs when cGMP binds to the allosteric site that exposes serine and permits phosphorylation. The results for the phosphorylation of serine leads to increased cGMP hydrolysis at the catalytic domain. The affinity of the catalytic domain for cGMP increases and further increases the PDE5 catalytic domain activity. [33]
In its Fe(II) form, this heme moiety is the target of nitric oxide, which is synthesized by endothelial cells following appropriate stimulation. Binding of nitric oxide to the heme results in activation of the C-terminal catalytic domain, which produces cGMP from GTP.
In mammalian cells, cGAMP is synthesized by cyclic GMP-AMP synthase from ATP and GTP upon cytosolic DNA stimulation. [2] cGAMP produced by cGAS contains mixed phosphodiester linkages, with one between 2'-OH of GMP and 5'-phosphate of AMP and the other between 3'-OH of AMP and 5'-phosphate of GMP. [3] [4] [5] [6]
The binding of ANP to its receptor causes the conversion of GTP to cGMP and raises intracellular cGMP. As a consequence, cGMP activates a cGMP-dependent kinase ( PKG or cGK) that phosphorylates proteins at specific serine and threonine residues.
There are three basic types of secondary messenger molecules: [citation needed] Hydrophobic molecules: water-insoluble molecules such as diacylglycerol, and phosphatidylinositols, which are membrane-associated and diffuse from the plasma membrane into the intermembrane space where they can reach and regulate membrane-associated effector proteins.
ANP activation of the ANP catalytic receptor will stimulate its intracellular guanylyl cyclase activity to convert GTP to cGMP. cGMP will then stimulate cGMP-dependent protein kinase (PKG), which will then induce smooth muscle relaxation. This is particularly important in the vasculature, where vascular smooth muscle will bind ANP released as a ...