{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T07:08:04Z","timestamp":1784012884017,"version":"3.55.0"},"reference-count":50,"publisher":"National Academy of Sciences","issue":"39","license":[{"start":{"date-parts":[[2022,9,19]],"date-time":"2022-09-19T00:00:00Z","timestamp":1663545600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100006955","name":"HHS | NIH | Office of Extramural Research, National Institutes of Health","doi-asserted-by":"publisher","award":["GM135315"],"award-info":[{"award-number":["GM135315"]}],"id":[{"id":"10.13039\/100006955","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006955","name":"HHS | NIH | Office of Extramural Research, National Institutes of Health","doi-asserted-by":"publisher","award":["GM125924"],"award-info":[{"award-number":["GM125924"]}],"id":[{"id":"10.13039\/100006955","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","award":["1643814"],"award-info":[{"award-number":["1643814"]}],"id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2022,9,27]]},"abstract":"<jats:p>\n                    Chlamydia protein associating with death domains (CADD) is involved in the biosynthesis of\n                    <jats:italic>para<\/jats:italic>\n                    -aminobenzoate (pABA), an essential component of the folate cofactor that is required for the survival and proliferation of the human pathogen\n                    <jats:italic>Chlamydia trachomatis<\/jats:italic>\n                    . The pathway used by\n                    <jats:italic>Chlamydiae<\/jats:italic>\n                    for pABA synthesis differs from the canonical multi-enzyme pathway used by most bacteria that relies on chorismate as a metabolic precursor. Rather, recent work showed pABA formation by CADD derives from\n                    <jats:sc>l<\/jats:sc>\n                    -tyrosine. As a member of the emerging superfamily of heme oxygenase\u2013like diiron oxidases (HDOs), CADD was proposed to use a diiron cofactor for catalysis. However, we report maximal pABA formation by CADD occurs upon the addition of both iron and manganese, which implicates a heterobimetallic Fe:Mn cluster is the catalytically active form. Isotopic labeling experiments and proteomics studies show that CADD generates pABA from a protein-derived tyrosine (Tyr27), a residue that is \u223c14 \u00c5 from the dimetal site. We propose that this self-sacrificial reaction occurs through O\n                    <jats:sub>2<\/jats:sub>\n                    activation by a probable Fe:Mn cluster through a radical relay mechanism that connects to the \u201csubstrate\u201d Tyr, followed by amination and direct oxygen insertion. These results provide the molecular basis for pABA formation in\n                    <jats:italic>C. trachomatis<\/jats:italic>\n                    , which will inform the design of novel therapeutics.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2210908119","type":"journal-article","created":{"date-parts":[[2022,9,19]],"date-time":"2022-09-19T15:16:45Z","timestamp":1663600605000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":33,"title":["Self-sacrificial tyrosine cleavage by an Fe:Mn oxygenase for the biosynthesis of\n                    <i>para<\/i>\n                    -aminobenzoate in\n                    <i>Chlamydia trachomatis<\/i>"],"prefix":"10.1073","volume":"119","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1993-6541","authenticated-orcid":false,"given":"Olivia M.","family":"Manley","sequence":"first","affiliation":[{"name":"Department of Molecular and Structural Biochemistry, North Carolina State 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