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Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2025,12,2]]},"abstract":"<jats:p>\n                    CutA, a conserved protein across all domains of life, has been suggested to be involved in copper tolerance in bacteria, though recent studies have questioned this association, leaving its biological role unknown. To clarify its function, we studied\n                    <jats:italic toggle=\"yes\">cutA<\/jats:italic>\n                    knockout mutants from two phylogenetically distant species,\n                    <jats:italic toggle=\"yes\">Synechococcus elongatus PCC 7942<\/jats:italic>\n                    and\n                    <jats:italic toggle=\"yes\">\n                      <jats:italic toggle=\"yes\">Escherichia coli<\/jats:italic>\n                    <\/jats:italic>\n                    , using phenotyping combined with metabolomics. To investigate the interaction of CutA with potential substrates and cofactors, we performed a series of native metabolomics experiments with CutA and cell extracts from which we identified the lumazine 2\u2019-deoxyxanthopterin B2, a previously uncharacterized pteridine, to bind CutA in both species. Based on these results, we identified a set of other pteridines, including the essential cofactor tetrahydrobiopterin, as ligands of CutA. In the presence of pterins, we observed an increased affinity of CutA for copper ions. In addition,\n                    <jats:italic toggle=\"yes\">\n                      <jats:italic toggle=\"yes\">E. coli<\/jats:italic>\n                    <\/jats:italic>\n                    CutA mutants exhibited decreased copper resistance. These findings, alongside the known role of pteridines as redox shuttles, suggest a previously unrecognized role for CutA in coordinating cellular copper homeostasis and redox balance via pteridine metabolism.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2509468122","type":"journal-article","created":{"date-parts":[[2025,11,25]],"date-time":"2025-11-25T19:02:44Z","timestamp":1764097364000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":3,"title":["Native metabolomics identifies pteridines as CutA ligands and modulators of copper binding"],"prefix":"10.1073","volume":"122","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7691-7531","authenticated-orcid":false,"given":"Berenike C.","family":"Wagner","sequence":"first","affiliation":[{"name":"Department of Organismic Interactions, Interfaculty Institute of Microbiology and Infection Medicine, University of T\u00fcbingen","place":["T\u00fcbingen, Germany"]},{"name":"Cluster 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