title: Oxidation and loss of heme in soluble guanylyl cyclase from Manduca sexta.
abstract: Oxidation and loss of heme in soluble guanylyl/guanylate cyclase (sGC), the nitric oxide receptor, is thought to be a major contributor to cardiovascular disease and is the target of compounds BAY 58-2667 and HMR1766. Using spectroelectrochemical titration, we found a truncated sGC to be highly stable in the ferrous state (234 mV) and to bind ferrous heme tightly even in the presence of NO, despite the NO-induced release of the proximal histidine. In contrast, oxidized sGC readily loses ferric heme to myoglobin (0.47 ± 0.02 h(-1)). Peroxynitrite, the presumed cellular oxidant, readily oxidizes sGC in 5 mM glutathione.
authors.affiliation: Department of Chemistry and Biochemistry, University of Arizona, Tucson, Arizona 85721, United States.
authors.forename: Bradley G
authors.initials: BG
authors.lastname: Fritz
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Hu
authors.forename: Jacqueline L
authors.initials: JL
authors.lastname: Brailey
authors.forename: Robert E
authors.initials: RE
authors.lastname: Berry
authors.forename: F Ann
authors.initials: FA
authors.lastname: Walker
authors.forename: William R
authors.initials: WR
authors.lastname: Montfort
mesh_terms: D000818:Animals; D006162:Guanylate Cyclase / Q000737:chemistry* / Q000378:metabolism*; D006418:Heme / Q000378:metabolism*; D007700:Kinetics; D018402:Manduca / Q000201:enzymology*; D010084:Oxidation-Reduction; D018160:Receptors, Cytoplasmic and Nuclear / Q000737:chemistry* / Q000378:metabolism*; D000071756:Soluble Guanylyl Cyclase
chemical_list: D018160:Receptors, Cytoplasmic and Nuclear; D006418:Heme; D006162:Guanylate Cyclase; D000071756:Soluble Guanylyl Cyclase