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FDPs are O<jats:sub>2<\/jats:sub> or NO reducing enzymes; for many pathogens, they help mitigate the NO produced by the immune system of the host, and aid survival during fluctuating concentrations concentrations of oxygen. FDPs have a mosaic structure, being predicted to contain multiple extra domains. <jats:italic>Clostridium difficile<\/jats:italic>, a threatening human pathogen, encodes two FDPs: one with the two canonical domains, and another with a larger polypeptide chain of 843 amino acids, CD1623, with two extra domains, predicted to be a short-rubredoxin-like and an NAD(P)H:rubredoxin oxidoreductase. This multi-domain protein is the most complex FDP characterized thus far. Each of the predicted domains was characterized and the presence of the predicted cofactors confirmed by biochemical and spectroscopic analysis. Results show that this protein operates as a standalone FDP, receiving electrons directly from NADH, and reducing oxygen to water, precluding the need for extra partners. CD1623 displayed negligible NO reductase activity, and is thus considered an oxygen selective FDP, that may contribute to the survival of <jats:italic>C. difficile<\/jats:italic> in the human gut and in the environment.<\/jats:p>","DOI":"10.1038\/s41598-018-28453-3","type":"journal-article","created":{"date-parts":[[2018,6,29]],"date-time":"2018-06-29T10:27:17Z","timestamp":1530268037000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":38,"title":["The multidomain flavodiiron protein from Clostridium difficile 630 is an NADH:oxygen oxidoreductase"],"prefix":"10.1038","volume":"8","author":[{"given":"Filipe","family":"Folgosa","sequence":"first","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0900-6287","authenticated-orcid":false,"given":"Maria C.","family":"Martins","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4124-6237","authenticated-orcid":false,"given":"Miguel","family":"Teixeira","sequence":"additional","affiliation":[]}],"member":"297","published-online":{"date-parts":[[2018,7,5]]},"reference":[{"key":"28453_CR1","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1007\/s00775-015-1329-4","volume":"21","author":"CV Romao","year":"2016","unstructured":"Romao, C. 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