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A persulfide\u2010specific chemoselective proteomics approach with mammalian cells has identified a broad range of zinc finger (ZF) proteins as targets of persulfidation. Parallel studies with isolated ZFs show that persulfidation is mediated by Zn<jats:sup>II<\/jats:sup>, O<jats:sub>2<\/jats:sub>, and H<jats:sub>2<\/jats:sub>S, with intermediates involving oxygen\u2010 and sulfur\u2010based radicals detected by mass spectrometry and optical spectroscopies. A small molecule Zn<jats:sup>II<\/jats:sup> complex exhibits analogous reactivity with H<jats:sub>2<\/jats:sub>S and O<jats:sub>2<\/jats:sub>, giving a persulfidated product. These data show that Zn<jats:sup>II<\/jats:sup> is not just a biological structural element, but also plays a critical role in mediating H<jats:sub>2<\/jats:sub>S\u2010dependent persulfidation. ZF persulfidation appears to be a general post\u2010translational modification and a possible conduit for H<jats:sub>2<\/jats:sub>S signaling. This work has implications for our understanding of H<jats:sub>2<\/jats:sub>S\u2010mediated signaling and the regulation of ZFs in cellular physiology and development.<\/jats:p>","DOI":"10.1002\/anie.202401003","type":"journal-article","created":{"date-parts":[[2024,5,29]],"date-time":"2024-05-29T11:25:43Z","timestamp":1716981943000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Chemoselective Proteomics, Zinc Fingers, and a Zinc(II) Model for H<sub>2<\/sub>S Mediated Persulfidation"],"prefix":"10.1002","volume":"63","author":[{"given":"Andrew T.","family":"Stoltzfus","sequence":"first","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":"Jasper G.","family":"Ballot","sequence":"additional","affiliation":[{"name":"Department of Chemistry Johns Hopkins University  3400\u2005N Charles Street Baltimore MD, 21218 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thibaut","family":"Vignane","sequence":"additional","affiliation":[{"name":"Leibniz-Institut f\u00fcr Analytische Wissenschaften\u2014ISAS\u2014e.V.  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