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Misregulation results in arthritis, sepsis and cancer, and there is an interest in modulating TTP activity with exogenous agents. Gold has anti\u2010inflammatory properties and has recently been shown to modulate the signaling pathway that produces TTP, suggesting that TTP may be a target of gold. The reactivity of [Au<jats:sup>III<\/jats:sup>(terpy)Cl]Cl<jats:sub>2<\/jats:sub> with TTP was investigated by UV\/Vis spectroscopy, spin\u2010filter inductively coupled plasma mass spectrometry, X\u2010ray absorption spectroscopy and native electrospray ionization mass spectrometry. Au<jats:sup>III<\/jats:sup> was found to replace zinc in the protein active site in the reduced Au<jats:sup>I<\/jats:sup> form, with the Au<jats:sup>I<\/jats:sup> ion coordinated to two cysteine residues in a linear geometry. The replacement of Zn<jats:sup>II<\/jats:sup> with Au<jats:sup>I<\/jats:sup> results in loss of both secondary structure and RNA binding function. In contrast, when Zn<jats:sup>II<\/jats:sup>TTP is bound to its RNA target, no replacement of Zn<jats:sup>II<\/jats:sup> with Au<jats:sup>I<\/jats:sup> is observed, even in the presence of excess Au<jats:sup>III<\/jats:sup>terpy. This discovery of differential reactivity of gold with TTP versus TTP\/RNA offers a potential strategy for selective targeting with gold complexes to control inflammation.<\/jats:p>","DOI":"10.1002\/chem.201904837","type":"journal-article","created":{"date-parts":[[2019,10,29]],"date-time":"2019-10-29T22:55:05Z","timestamp":1572389705000},"page":"1535-1547","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Role of Gold in Inflammation and Tristetraprolin Activity"],"prefix":"10.1002","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7724-8560","authenticated-orcid":false,"given":"Kiwon","family":"Ok","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Sciences University of Maryland School of Pharmacy  20 Penn St. Baltimore MD 21201 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5387-7004","authenticated-orcid":false,"given":"Wenjing","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences University of Maryland School of Pharmacy  20 Penn St. Baltimore MD 21201 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8204-7392","authenticated-orcid":false,"given":"Heather M.","family":"Neu","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences University of Maryland School of Pharmacy  20 Penn St. Baltimore MD 21201 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sharon","family":"Batelu","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences Wayne State University  259 Mack Avenue Detroit MI 48201 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6298-088X","authenticated-orcid":false,"given":"Timothy L.","family":"Stemmler","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences Wayne State University  259 Mack Avenue Detroit MI 48201 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5525-9170","authenticated-orcid":false,"given":"Maureen A.","family":"Kane","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences University of Maryland School of Pharmacy  20 Penn St. Baltimore MD 21201 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6366-2453","authenticated-orcid":false,"given":"Sarah L. 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