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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]
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]
Binding of nitric oxide to the heme results in activation of the C-terminal catalytic domain, which produces cGMP from GTP. The HNOX (Heme Nitric oxide/OXygen binding) domain of the beta subunit of sGC contains the prosthetic heme group, and is part of a family of related sensor proteins found throughout a wide range of organisms.
XMP is then converted into GMP by using the hydrolysis of 1 ATP and the conversion of glutamine to glutamate. [1] AMP and GMP can then be converted into ATP and GTP, respectively, by kinases that add additional phosphates. ATP stimulates production of GTP, while GTP stimulates production of ATP.
The G s alpha subunit of the stimulated G protein complex exchanges GDP for GTP and is released from the complex. [4] In a cAMP-dependent pathway, the activated G s alpha subunit binds to and activates an enzyme called adenylyl cyclase, which, in turn, catalyzes the conversion of ATP into cyclic adenosine monophosphate (cAMP). [5]
The enzyme 3′,5′-cyclic-GMP phosphodiesterase (EC 3.1.4.35) catalyzes the reaction guanosine 3′,5′-cyclic phosphate + H 2 O ⇌ {\displaystyle \rightleftharpoons } guanosine 5′-phosphate This enzyme belongs to the family of hydrolases , specifically those acting on phosphoric diester bonds.
Guanylyl transferases are enzymes that transfer a guanosine mono phosphate group, usually from GTP to another molecule, releasing pyrophosphate.Many eukaryotic guanylyl transferases are capping enzymes that catalyze the formation of the 5' cap in the co-transcriptional modification of messenger RNA.