Guanylate cyclase subunits

Fig. 4.1. Cellular model illustrating cell types in vascular wall involved in vasorelaxation induced by SERMs. Putative targets of SERMs are indicated within cyan tags. SERMs directly affect L-type VDCC, BK fil subunit in smooth muscle cells, and ER in endothelial cells. L-type VDCC L-type voltage-dependent calcium channel BK calcium-activated large conductance K+ channel PKG protein kinase G eNOS endothelial nitric oxide synthase GC soluble guanylate cyclase cGMP cyclic GM P V electrochemical membrane potential ER estrogen receptor. See text for further details...

Guanylate cyclases, which form cyclic GMP, occur in particulate and soluble forms.908 The latter have been of great interest because they are activated by nitric oxide (NO). The soluble guanylate cyclases are a(3 heterodimers. The C-terminal regions of both a and (3 subunits are homologous to the catalytic domain of adenylate cyclase. The N-terminal domain of the a subunits contains heme whose Fe atom is coordinated... 

Figure 3 Soluble guanylate cyclase, (a). Domain architecture of sCC. sGC consists of two homologous subunits, al and pi. Each subunit contains an N-terminal H-NOX domain, a central predicted PAS-like region, and a C-terminal catalytic domain. Heme (gray parallelogram) binds to the H-NOX domain on the pi subunit, (b). NO activation of sGC. NO binds to the sCC heme, which leads to the formation of a 5-coordinate ferrous nitrosyl complex and activates the protein several-hundred-fold above the basal level.

Buechler, W. A., Nakane, M., and Murad, F. (1991). Expression of soluble guanylate cyclase activity requires both enzyme subunits. Biochem. Biophys. Res. Commun. 174, 351-357. 

Guanylate cyclase [GTP pyrophosphate-lyase (cyclizing) EC 4.6.1.2.] can be purified as soluble and particulate isozyme forms from most mammalian tissues. While both isozyme families catalyze the formation of cGMP from GTP, they are structurally different proteins. Their mechanism of activation and their kinetic and physicochemical properties differ markedly from each other. Soluble guanylate cyclase (sGC) has been shown to exist as a heterodimer with protein subunits of 70 and 82 kDa and has a native... 

This toxin subunit is an enzyme, an ADP-ribo-syltransferase which catalyzes transfer of ADP-ribosyl units from the coenzyme NAD+ to specific arginine side chains to form N-ADP-ribosyl derivatives of various proteins. Of the proteins modified by cholera toxin, the most significant is the guanyl nucleotide regulatory protein Gs of the adenylate cyclase system.C/f/h ADP ribosylation of arginine 201 of the a subunit of protein Gs inhibits the GTP hydrolysis that normally allows the protein to relax to an unactivated form.e The ADP-ribosylated Gs keeps adenylate cyclase activated continuously and... 

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