Guanylate cyclase
FunctionGuanylate cyclase. (GC) catalyse the conversion of GTP to cGMP and pyrophosphate. cGMP is a second messenger that modulates various processes like platelet aggregation, neurotransmission, sexual arousal, gut peristalsis, blood pressure and more[1]. DiseaseMutations in retinal GC are involved in inherited retinopathy[2]. RelevanceA GC activator - Cinaciguat - is investigated as add-on to therapy of patients suffering from acute heart failure syndrome[3], [4]. Structural highlightsThe 3D structure of of human GC subunit α-1 complex with subunit β-1 and the activator cinaciguat shows the and replacing the haem. The activator makes various interactions with the β-1 subunit[5]. 3D structures of granulate cyclase |
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ReferencesReferences
- ↑ Potter LR. Guanylyl cyclase structure, function and regulation. Cell Signal. 2011 Dec;23(12):1921-6. doi: 10.1016/j.cellsig.2011.09.001. Epub, 2011 Sep 10. PMID:21914472 doi:http://dx.doi.org/10.1016/j.cellsig.2011.09.001
- ↑ Perrault I, Rozet JM, Calvas P, Gerber S, Camuzat A, Dollfus H, Chatelin S, Souied E, Ghazi I, Leowski C, Bonnemaison M, Le Paslier D, Frezal J, Dufier JL, Pittler S, Munnich A, Kaplan J. Retinal-specific guanylate cyclase gene mutations in Leber's congenital amaurosis. Nat Genet. 1996 Dec;14(4):461-4. doi: 10.1038/ng1296-461. PMID:8944027 doi:http://dx.doi.org/10.1038/ng1296-461
- ↑ Gheorghiade M, Greene SJ, Filippatos G, Erdmann E, Ferrari R, Levy PD, Maggioni A, Nowack C, Mebazaa A. Cinaciguat, a soluble guanylate cyclase activator: results from the randomized, controlled, phase IIb COMPOSE programme in acute heart failure syndromes. Eur J Heart Fail. 2012 Sep;14(9):1056-66. doi: 10.1093/eurjhf/hfs093. Epub 2012, Jun 19. PMID:22713287 doi:http://dx.doi.org/10.1093/eurjhf/hfs093
- ↑ Stasch JP, Pacher P, Evgenov OV. Soluble guanylate cyclase as an emerging therapeutic target in cardiopulmonary disease. Circulation. 2011 May 24;123(20):2263-73. doi: 10.1161/CIRCULATIONAHA.110.981738. PMID:21606405 doi:http://dx.doi.org/10.1161/CIRCULATIONAHA.110.981738
- ↑ Liu R, Kang Y, Chen L. Activation mechanism of human soluble guanylate cyclase by stimulators and activators. Nat Commun. 2021 Sep 17;12(1):5492. doi: 10.1038/s41467-021-25617-0. PMID:34535643 doi:http://dx.doi.org/10.1038/s41467-021-25617-0