title: Studying the structure and regulation of soluble guanylyl cyclase.
abstract: Soluble guanylyl cyclase acts as the receptor for the signaling molecule nitric oxide. The enzyme consists of two different subunits. Each subunit shows the cyclase catalytic domain, which is also conserved in the membrane-bound guanylyl cyclases and the adenylyl cyclases. The N-terminal regions of the subunits are responsible for binding of the prosthetic heme group of the enzyme, which is required for the stimulatory effect of nitric oxide (NO). The five-coordinated ferrous heme displays a histidine as the axial ligand; activation of soluble guanylyl cyclase by NO is initiated by binding of NO to the heme iron and proceeds via breaking of the histidine-to-iron bond. Recently, a novel pharmacological and possibly physiological principle of guanylyl cyclase sensitization was demonstrated. The substance YC-1 has been shown to activate the enzyme independent of NO, to potentiate the effect of submaximally effective NO concentrations, and to turn carbon monoxide into an effective activator of soluble guanylyl cyclase.
authors.affiliation: Institut für Pharmakologie, Freie Universität Berlin, Thielallee 67-73, Berlin, D-14195, Federal Republic of Germany.
authors.forename: D
authors.initials: D
authors.lastname: Koesling
mesh_terms: D000818:Animals; D001671:Biochemistry / Q000379:methods; D003545:Cysteine / Q000235:genetics; D004252:DNA Mutational Analysis; D004789:Enzyme Activation; D006162:Guanylate Cyclase / Q000737:chemistry* / Q000302:isolation & purification / Q000502:physiology*; D006418:Heme; D006639:Histidine / Q000235:genetics; D007527:Isoenzymes / Q000737:chemistry / Q000302:isolation & purification; D012995:Solubility
chemical_list: D007527:Isoenzymes; D006418:Heme; D006639:Histidine; D006162:Guanylate Cyclase; D003545:Cysteine