title: Tonic and acute nitric oxide signaling through soluble guanylate cyclase is mediated by nonheme nitric oxide, ATP, and GTP.
abstract: Nitric oxide (NO) affects many physiological systems by activating cGMP signaling cascades through soluble guanylate cyclase (sGC). In the accepted model, NO binds to the sGC heme, activating the enzyme. Here, we report that in the presence of physiological concentrations of ATP and GTP, NO dissociation from the sGC heme is approximately 160 times slower than the rate of enzyme deactivation in vitro. Deactivated sGC still has NO bound to the heme, and full activation requires additional NO. We propose an activation model where, in the presence of both ATP and GTP, tonic NO forms a stable heme complex with low sGC activity; acute production of NO transiently and fully activates this NO-bound sGC.
authors.affiliation: Department of Biological Chemistry, University of Michigan, Ann Arbor, MI 48109, USA.
authors.forename: Stephen P L
authors.initials: SP
authors.lastname: Cary
authors.forename: Jonathan A
authors.initials: JA
authors.lastname: Winger
authors.forename: Michael A
authors.initials: MA
authors.lastname: Marletta
mesh_terms: D000255:Adenosine Triphosphate; D000818:Animals; D004789:Enzyme Activation; D006160:Guanosine Triphosphate; D006162:Guanylate Cyclase / Q000378:metabolism*; D006418:Heme / Q000378:metabolism; D007700:Kinetics; D008956:Models, Chemical; D009569:Nitric Oxide / Q000378:metabolism* / Q000502:physiology; D051381:Rats; D015398:Signal Transduction; D012995:Solubility
chemical_list: D009569:Nitric Oxide; D006418:Heme; D006160:Guanosine Triphosphate; D000255:Adenosine Triphosphate; D006162:Guanylate Cyclase