title: Persulfide reactivity in the detection of protein s-sulfhydration.
abstract: Hydrogen sulfide (H2S) has emerged as a new member of the gaseous transmitter family of signaling molecules and appears to play a regulatory role in the cardiovascular and nervous systems. Recent studies suggest that protein cysteine S-sulfhydration may function as a mechanism for transforming the H2S signal into a biological response. However, selective detection of S-sulfhydryl modifications is challenging since the persulfide group (RSSH) exhibits reactivity akin to other sulfur species, especially thiols. A modification of the biotin switch technique, using S-methyl methanethiosulfonate (MMTS) as an alkylating reagent, was recently used to identify a large number of proteins that may undergo S-sulfhydration, but the underlying mechanism of chemical detection was not fully explored. To address this key issue, we have developed a protein persulfide model and analogue of MMTS, S-4-bromobenzyl methanethiosulfonate (BBMTS). Using these new reagents, we investigated the chemistry in the modified biotin switch method and examined the reactivity of protein persulfides toward different electrophile/nucleophile species. Together, our data affirm the nucleophilic properties of the persulfide sulfane sulfur and afford new insights into protein S-sulfhydryl chemistry, which may be exploited in future detection strategies.
authors.affiliation: Department of Chemistry, The Scripps Research Institute , Jupiter, Florida 33456, United States.
authors.forename: Jia
authors.initials: J
authors.lastname: Pan
authors.forename: Kate S
authors.initials: KS
authors.lastname: Carroll
mesh_terms: D000477:Alkylating Agents / Q000737:chemistry; D001671:Biochemistry / Q000379:methods; D001710:Biotin / Q000737:chemistry; D006862:Hydrogen Sulfide / Q000737:chemistry; D008698:Mesylates / Q000737:chemistry; D008741:Methyl Methanesulfonate / Q000031:analogs & derivatives / Q000737:chemistry; D017293:Protein S / Q000737:chemistry*; D013438:Sulfhydryl Compounds / Q000032:analysis; D013440:Sulfides / Q000032:analysis*
chemical_list: D000477:Alkylating Agents; D008698:Mesylates; D017293:Protein S; D013438:Sulfhydryl Compounds; D013440:Sulfides; C051552:persulfides; C014674:methyl methanethiosulfonate; C074502:methanethiosulfonate; D001710:Biotin; D008741:Methyl Methanesulfonate; D006862:Hydrogen Sulfide
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