Structural insights into the regulation and the activation mechanism of mammalian guanylyl cyclases

Molecular Variants of Soluble Guanylyl Cyclase Affecting Cardiovascular Risk

“…52 This linear transmission model disagrees with the findings from Winger et al, 53 who showed that the isolated H-NOX domain can directly interact with the isolated catalytic region of sGC. Consistent with those results, Haase et al demonstrated the N-termini of sGC being in close proximity to the C-termini using fluorescence resonance energy transfer (FRET).…”

Nitric Oxide Activation of Guanylate Cyclase Pushes the α1 Signaling Helix and the β1 Heme-binding Domain Closer to the Substrate-binding Site

“…In transmembrane forms similar to GC-A, the extracellular binding of the ligand ANP to preformed homodimers is transmitted across the transmembrane helices and reorients the two intracellular domains into the active conformation (3). By analogy, it was assumed that binding of NO to the amino-terminal heme NO binding (HNOX) domain is communicated to the carboxylterminal catalytic domain through the coiled-coil domain (4). This linear model of NO activation has been questioned by findings that the isolated HNOX domain can directly interact with the isolated catalytic region of NOsGC (5).…”

Cyclic Guanosine Monophosphate Compartmentation in Rat Cardiac Myocytes

“…3-5 cGMP synthesis is controlled by 2 types of guanylyl cyclases (GC) that differ in their cellular location and activation by specific ligands: a particulate GC (pGC) present at the plasma membrane, which is activated by natriuretic peptides such as atrial (ANP), brain (BNP), and C-type natriuretic peptide 6 -8 ; and a soluble guanylyl cyclase (sGC) present in the cytosol and activated by nitric oxide (NO). 8,9 Clinical Perspective p 2228Although NO and natriuretic peptides use cGMP as a common second messenger, there are many instances in which activation of pGC and sGC leads to different functional effects. 10 -14 One explanation for these divergent effects is that cGMP rises in specific subcellular locations, regulating different targets in different parts of the cell.…”

“…[3][4][5] cGMP synthesis is controlled by 2 types of guanylyl cyclases (GC) that differ in their cellular location and activation by specific ligands: a particulate GC (pGC) present at the plasma membrane, which is activated by natriuretic peptides such as atrial (ANP), brain (BNP), and C-type natriuretic peptide 6 -8 ; and a soluble guanylyl cyclase (sGC) present in the cytosol and activated by nitric oxide (NO). 8,9 Clinical Perspective p 2228…”