{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T02:45:18Z","timestamp":1791773118651,"version":"4.3.4"},"reference-count":69,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,10,11]],"date-time":"2026-10-11T00:00:00Z","timestamp":1791676800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,10,11]],"date-time":"2026-10-11T00:00:00Z","timestamp":1791676800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["GM158411"],"award-info":[{"award-number":["GM158411"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","award":["0922862"],"award-info":[{"award-number":["0922862"]}],"id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Angew Chem Int Ed"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Posttranslational sulfur incorporation into peptide backbones is increasingly reported. These efforts broaden our understanding of thioamides, which have distinct conformational and hydrogen\u2010bonding properties compared with amides. YcaO\u2010catalyzed thioamidation of the ribosomal protein uL16 reportedly occurs across thousands of Pseudomonadota. Here, we identify the cysteine desulfurase IscS, a crucial component of iron\u2013sulfur cluster assembly, as the direct sulfur donor for uL16 thioamidation. Genetic deletion, in vitro reconstitution, kinetic analysis, sulfide scavenging, and mutational studies support this conclusion. Our data support a mechanism in which the IscS persulfide attacks the\n                    <jats:italic>O<\/jats:italic>\n                    \u2010phosphorylated uL16 backbone amide to form an IscS\u2013uL16 disulfide intermediate. This labile disulfide is rapidly reduced, and the resulting hemiorthothioamide collapses with phosphate release to give the thioamide. IscS binds uL16 with mid\u2010nanomolar affinity and can be displaced by other IscS\u2010dependent sulfur acceptors. IscS promotes formation of the 2:2 YcaO\u2013uL16 complex from the otherwise predominant 1:1 complex. Structural and mutational studies identify uL16 residues important for catalytically competent enzyme\u2013substrate interactions. These findings define the sulfur delivery pathway for uL16 thioamidation and reveal an additional role of the IscS persulfide beyond iron\u2013sulfur cluster assembly, suggesting it serves as another nucleophile for YcaO\u2010catalyzed backbone modification.\n                  <\/jats:p>","DOI":"10.1002\/anie.2523475","type":"journal-article","created":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T02:22:39Z","timestamp":1791771759000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["An IscS Persulfide Donates the Sulfur for Ribosomal Protein uL16 Thioamidation"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1820-1997","authenticated-orcid":false,"given":"Yanqing","family":"Xue","sequence":"first","affiliation":[{"name":"Department of Biochemistry Vanderbilt University School of Medicine Basic Sciences  Nashville Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markus W.","family":"Voehler","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Center for Structural Biology Vanderbilt University  Nashville Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9564-0953","authenticated-orcid":false,"given":"Douglas A.","family":"Mitchell","sequence":"additional","affiliation":[{"name":"Department of Biochemistry Vanderbilt University School of Medicine Basic Sciences  Nashville Tennessee USA"},{"name":"Department of Chemistry and Center for Structural Biology Vanderbilt University  Nashville Tennessee 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