{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T03:19:42Z","timestamp":1791083982019,"version":"4.1.0"},"reference-count":59,"publisher":"National Academy of Sciences","issue":"6","license":[{"start":{"date-parts":[[2026,2,2]],"date-time":"2026-02-02T00:00:00Z","timestamp":1769990400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000864","name":"Michael J. Fox Foundation for Parkinson\u2019s Research","doi-asserted-by":"publisher","award":["MJFF-008730"],"award-info":[{"award-number":["MJFF-008730"]}],"id":[{"id":"10.13039\/100000864","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Gisela and Dennis Alter Endowed Chair in Pediatric Neonatology and Stoke Investigator Funds","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2026,2,10]]},"abstract":"<jats:p>\n                    Tyrosine nitration alters the structure, function, and cellular localization of proteins and is implicated in the pathology of multiple diseases [G. Ferrer-Sueta\n                    <jats:italic toggle=\"yes\">et al.<\/jats:italic>\n                    ,\n                    <jats:italic toggle=\"yes\">Chem. Rev.<\/jats:italic>\n                    <jats:bold>118<\/jats:bold>\n                    , 1338\u20131408 (2018), H. Ischiropoulos,\n                    <jats:italic toggle=\"yes\">Arch. Biochem. Biophys.<\/jats:italic>\n                    <jats:bold>356<\/jats:bold>\n                    , 1\u201311 (1998), I. Griswold-Prenner\n                    <jats:italic toggle=\"yes\">et al.<\/jats:italic>\n                    ,\n                    <jats:italic toggle=\"yes\">J. Biol. Chem.<\/jats:italic>\n                    <jats:bold>299<\/jats:bold>\n                    , 105038\u201310554 (2023)]. Although protein nitration is assumed to proceed via nonspecific chemical mechanisms, it is highly selective, suggesting the possibility of enzymatic catalysis. Here, we showed that glyoxalase domain-containing protein 4 (GLOD4), a previously uncharacterized protein, is an enzyme that catalyzes selective protein nitration. A primary in vivo target for GLOD4-mediated nitration is alpha-synuclein (\u03b1-syn), which is central to the pathogenesis of Parkinson\u2019s disease (PD) and related disorders. We document tyrosine nitration of \u03b1-syn by GLOD4 in vitro, in cells, and in a murine model of synuclein pathology. The data identified a function of GLOD4 and other structurally related proteins that catalyze the peroxynitrite-mediated selective protein tyrosine nitration. This enzymatic catalysis of nitration may unearth pathophysiological mechanisms and potential interventions in diseases such as PD, cancer, and autoimmunity.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2515002123","type":"journal-article","created":{"date-parts":[[2026,2,2]],"date-time":"2026-02-02T20:07:36Z","timestamp":1770062856000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":3,"title":["Selective peroxynitrite-mediated protein nitration catalyzed by glyoxalase domain containing protein 4"],"prefix":"10.1073","volume":"123","author":[{"given":"Sarah","family":"Wright","sequence":"first","affiliation":[{"name":"Nitrase Therapeutics","place":["Brisbane"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vu C.","family":"Dang","sequence":"additional","affiliation":[{"name":"Nitrase 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