title: Sulfhydration mediates neuroprotective actions of parkin.
abstract: Increases in S-nitrosylation and inactivation of the neuroprotective ubiquitin E3 ligase, parkin, in the brains of patients with Parkinson's disease are thought to be pathogenic and suggest a possible mechanism linking parkin to sporadic Parkinson's disease. Here we demonstrate that physiologic modification of parkin by hydrogen sulfide, termed sulfhydration, enhances its catalytic activity. Sulfhydration sites are identified by mass spectrometry analysis and are investigated by site-directed mutagenesis. Parkin sulfhydration is markedly depleted in the brains of patients with Parkinson's disease, suggesting that this loss may be pathologic. This implies that hydrogen sulfide donors may be therapeutic.
authors.affiliation: Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
authors.forename: M Scott
authors.initials: MS
authors.lastname: Vandiver
authors.forename: Bindu D
authors.initials: BD
authors.lastname: Paul
authors.forename: Risheng
authors.initials: R
authors.lastname: Xu
authors.forename: Senthilkumar
authors.initials: S
authors.lastname: Karuppagounder
authors.forename: Feng
authors.initials: F
authors.lastname: Rao
authors.forename: Adele M
authors.initials: AM
authors.lastname: Snowman
authors.forename: Han Seok
authors.initials: HS
authors.lastname: Ko
authors.forename: Yun Il
authors.initials: YI
authors.lastname: Lee
authors.forename: Valina L
authors.initials: VL
authors.lastname: Dawson
authors.forename: Ted M
authors.initials: TM
authors.lastname: Dawson
authors.forename: Nilkantha
authors.initials: N
authors.lastname: Sen
authors.forename: Solomon H
authors.initials: SH
authors.lastname: Snyder
mesh_terms: D000595:Amino Acid Sequence; D002384:Catalysis; D006862:Hydrogen Sulfide / Q000494:pharmacology; D013058:Mass Spectrometry; D008969:Molecular Sequence Data; D018696:Neuroprotective Agents / Q000378:metabolism*; D009603:Nitroso Compounds / Q000378:metabolism; D013438:Sulfhydryl Compounds / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*
chemical_list: D018696:Neuroprotective Agents; D009603:Nitroso Compounds; D013438:Sulfhydryl Compounds; D044767:Ubiquitin-Protein Ligases; C111567:parkin protein; D006862:Hydrogen Sulfide
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