title: Direct and nitroxyl (HNO)-mediated reactions of acyloxy nitroso compounds with the thiol-containing proteins glyceraldehyde 3-phosphate dehydrogenase and alkyl hydroperoxide reductase subunit C.
abstract: Nitroxyl (HNO) reacts with thiols, and this reactivity requires the use of donors with 1-nitrosocyclohexyl acetate, pivalate, and trifluoroacetate, forming a new group. These acyloxy nitroso compounds inhibit glyceraldehyde 3-phosphate dehydrogenase (GAPDH) by forming a reduction reversible active site disulfide and a reduction irreversible sulfinic acid or sulfinamide modification at Cys244. Addition of these acyloxy nitroso compounds to AhpC C165S yields a sulfinic acid and sulfinamide modification. A potential mechanism for these transformations includes nucleophilic addition of the protein thiol to a nitroso compound to yield an N-hydroxysulfenamide, which reacts with thiol to give disulfide or rearranges to sulfinamides. Known HNO donors produce the unsubstituted protein sulfinamide as the major product, while the acetate and pivalate give substituted sulfinamides that hydrolyze to sulfinic acids. These results suggest that nitroso compounds form a general class of thiol-modifying compounds, allowing their further exploration.
authors.affiliation: Department of Chemistry and ‡Department of Physics, Wake Forest University , Winston-Salem, North Carolina 27109, United States.
authors.forename: Susan
authors.initials: S
authors.lastname: Mitroka
authors.forename: Mai E
authors.initials: ME
authors.lastname: Shoman
authors.forename: Jenna F
authors.initials: JF
authors.lastname: DuMond
authors.forename: Landon
authors.initials: L
authors.lastname: Bellavia
authors.forename: Omar M
authors.initials: OM
authors.lastname: Aly
authors.forename: Mohamed
authors.initials: M
authors.lastname: Abdel-Aziz
authors.forename: Daniel B
authors.initials: DB
authors.lastname: Kim-Shapiro
authors.forename: S Bruce
authors.initials: SB
authors.lastname: King
mesh_terms: D000595:Amino Acid Sequence; D002853:Chromatography, Liquid; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000037:antagonists & inhibitors / Q000737:chemistry*; D013058:Mass Spectrometry; D008969:Molecular Sequence Data; D009589:Nitrogen Oxides / Q000737:chemistry*; D009603:Nitroso Compounds / Q000737:chemistry*; D054464:Peroxiredoxins / Q000737:chemistry*; D013438:Sulfhydryl Compounds / Q000737:chemistry*
chemical_list: D009589:Nitrogen Oxides; D009603:Nitroso Compounds; D013438:Sulfhydryl Compounds; D054464:Peroxiredoxins; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases; C039900:nitroxyl
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