title: The effects of nitroxyl (HNO) on soluble guanylate cyclase activity: interactions at ferrous heme and cysteine thiols.
abstract: It has been previously proposed that nitric oxide (NO) is the only biologically relevant nitrogen oxide capable of activating the enzyme soluble guanylate cyclase (sGC). However, recent reports implicate HNO as another possible activator of sGC. Herein, we examine the affect of HNO donors on the activity of purified bovine lung sGC and find that, indeed, HNO is capable of activating this enzyme. Like NO, HNO activation appears to occur via interaction with the regulatory ferrous heme on sGC. Somewhat unexpectedly, HNO does not activate the ferric form of the enzyme. Finally, HNO-mediated cysteine thiol modification appears to also affect enzyme activity leading to inhibition. Thus, sGC activity can be regulated by HNO via interactions at both the regulatory heme and cysteine thiols.
authors.affiliation: Department of Chemistry and Biochemistry, University of California, Los Angeles, California 90095.
authors.forename: Thomas W
authors.initials: TW
authors.lastname: Miller
authors.affiliation: the Department of Chemistry, University of Wisconsin, Madison, Wisconsin 53706.
authors.forename: Melisa M
authors.initials: MM
authors.lastname: Cherney
authors.affiliation: the Department of Chemistry, University of Wisconsin, Madison, Wisconsin 53706.
authors.forename: Andrea J
authors.initials: AJ
authors.lastname: Lee
authors.affiliation: Department of Chemistry and Biochemistry, University of California, Los Angeles, California 90095.
authors.forename: Nestor E
authors.initials: NE
authors.lastname: Francoleon
authors.affiliation: the Department of Chemistry, University of California, Irvine, California 92697.
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Farmer
authors.affiliation: the Department of Chemistry, Wake Forest University, Winston Salem, North Carolina 27109.
authors.forename: S Bruce
authors.initials: SB
authors.lastname: King
authors.affiliation: Department of Pharmacology, University College London, Medical Sciences Building, Gower Street, London WC1E 6BT, United Kingdom.
authors.forename: Adrian J
authors.initials: AJ
authors.lastname: Hobbs
authors.affiliation: the Department of Chemistry, University of Arizona, Tucson, Arizona 85721.
authors.forename: Katrina M
authors.initials: KM
authors.lastname: Miranda
authors.affiliation: the Department of Chemistry, University of Wisconsin, Madison, Wisconsin 53706.
authors.forename: Judith N
authors.initials: JN
authors.lastname: Burstyn
authors.affiliation: the Department of Chemistry, Sonoma State University, Rohnert Park, California 94928-3609.
authors.forename: Jon M
authors.initials: JM
authors.lastname: Fukuto
mesh_terms: D000818:Animals; D001665:Binding Sites; D002417:Cattle; D003545:Cysteine / Q000737:chemistry*; D004305:Dose-Response Relationship, Drug; D006162:Guanylate Cyclase / Q000378:metabolism*; D006418:Heme / Q000737:chemistry*; D007501:Iron / Q000737:chemistry; D008168:Lung / Q000378:metabolism; D008954:Models, Biological; D008956:Models, Chemical; D009569:Nitric Oxide / Q000737:chemistry; D009589:Nitrogen Oxides / Q000494:pharmacology*; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D000071756:Soluble Guanylyl Cyclase; D013438:Sulfhydryl Compounds / Q000737:chemistry*; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D009589:Nitrogen Oxides; D018160:Receptors, Cytoplasmic and Nuclear; D013438:Sulfhydryl Compounds; D014665:Vasodilator Agents; D009569:Nitric Oxide; D006418:Heme; D007501:Iron; D006162:Guanylate Cyclase; D000071756:Soluble Guanylyl Cyclase; C039900:nitroxyl; D003545:Cysteine