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One family of proteins modified by H<jats:sub>2<\/jats:sub>S are zinc finger (ZF) proteins, which contain multiple zinc\u2010coordinating cysteine residues. Herein, we report the reactivity of H<jats:sub>2<\/jats:sub>S with a ZF protein called tristetraprolin (TTP). Rapid persulfidation leading to complete thiol oxidation of TTP mediated by H<jats:sub>2<\/jats:sub>S was observed by low\u2010temperature ESI\u2010MS and fluorescence spectroscopy. Persulfidation of TTP required O<jats:sub>2<\/jats:sub>\u2009, which reacts with H<jats:sub>2<\/jats:sub>S to form superoxide, as detected by ESI\u2010MS, a hydroethidine fluorescence assay, and EPR spin trapping. H<jats:sub>2<\/jats:sub>S was observed to inhibit TTP function (binding to TNF\u03b1 mRNA) by an in vitro fluorescence anisotropy assay and to modulate TNF\u03b1 in vivo. H<jats:sub>2<\/jats:sub>S was unreactive towards TTP when the protein was bound to RNA, thus suggesting a protective effect of RNA.<\/jats:p>","DOI":"10.1002\/anie.201900823","type":"journal-article","created":{"date-parts":[[2019,3,29]],"date-time":"2019-03-29T03:12:44Z","timestamp":1553829164000},"page":"7997-8001","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":50,"title":["Direct Zinc Finger Protein Persulfidation by H<sub>2<\/sub>S Is Facilitated by Zn<sup>2+<\/sup>"],"prefix":"10.1002","volume":"58","author":[{"given":"Mike","family":"Lange","sequence":"first","affiliation":[{"name":"Department of Chemistry and Pharmacy University of Erlangen-N\u00fcrnberg  91058 Erlangen Germany"},{"name":"Current address: Center for Biotechnology and Biomedicine Institute of Bioanalytical Chemistry Faculty of Chemistry and Mineralogy University of Leipzig  04103 Leipzig Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7724-8560","authenticated-orcid":false,"given":"Kiwon","family":"Ok","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences University of Maryland School of Pharmacy  20 Penn Street Baltimore MD 21201 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geoffrey D.","family":"Shimberg","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences University of Maryland School of Pharmacy  20 Penn Street Baltimore MD 21201 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Biljana","family":"Bursac","sequence":"additional","affiliation":[{"name":"CNRS, Institut de Biochimie et G\u00e9n\u00e9tique Cellulaires\u2014UMR5095 University of Bordeaux  33077 Bordeaux France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1888-5575","authenticated-orcid":false,"given":"Lajos","family":"Mark\u00f3","sequence":"additional","affiliation":[{"name":"Experimental and Clinical Research Center Charit\u00e9 Medical Faculty and Max Delbr\u00fcck Center (MDC) for Molecular Medicine  Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1651-3359","authenticated-orcid":false,"given":"Ivana","family":"Ivanovi\u0107\u2010Burmazovi\u0107","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Pharmacy University of Erlangen-N\u00fcrnberg  91058 Erlangen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6366-2453","authenticated-orcid":false,"given":"Sarah L. 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