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The ability of <jats:italic>Mycobacterium\u00a0tuberculosis<\/jats:italic> (Mtb) to enter into a dormant state has been considered integral to the success of this bacterium as a human pathogen. One of the key systems involved in regulating the entrance into dormancy is the differentially expressed in virulent strain sensor protein (DevS) [(dormancy survival sensor protein (DosS)]. However, the physiological signal for DevS has remained unclear since it was first shown to be a heme\u2010based sensor with conflicting reports on whether it is a redox or an oxygen sensor. To address this question and provide a better understanding of the electronic properties of this protein, we present here, for the first time, a series of spectroelectrochemistry measurements of the full\u2010length holo DevS in anaerobic conditions as well as bound to CO, NO, imidazole (Imz), cyanide, and O<jats:sub>2<\/jats:sub>. An interesting feature of this protein is its ability to bind Imz even in the ferrous state, implying small\u2010molecule analogues could be designed as potential regulators. Nonetheless, a midpoint potential (<jats:italic>E<\/jats:italic><jats:sub>m<\/jats:sub>) value of +10\u00a0mV [vs normal hydrogen electrode (NHE)] for DevS as measured under anaerobic conditions is much higher than the expected cytosolic potential for Mtb or even within stimulated macrophages (~\u00a0\u2212270 mV vs NHE), indicating this sensor works in a reduced ferrous state. These data, along with the high oxygen affinity and very slow auto\u2010oxidation rate of DevS, provides evidence that it is not a redox sensor. Overall, this study validates the biological function of DevS as an oxygen sensor directly involved in the dormancy\/latency of Mtb.<\/jats:p>","DOI":"10.1111\/febs.14974","type":"journal-article","created":{"date-parts":[[2019,6,29]],"date-time":"2019-06-29T14:03:50Z","timestamp":1561817030000},"page":"4278-4293","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["A spectroelectrochemical investigation of the heme\u2010based sensor DevS\u00a0from <i>Mycobacterium\u00a0tuberculosis<\/i>: a redox <i>versus<\/i> oxygen sensor"],"prefix":"10.1111","volume":"286","author":[{"given":"Giamwemberg A.","family":"Barreto","sequence":"first","affiliation":[{"name":"Laborat\u00f3rio de Bioinorg\u00e2nica Departamento de Qu\u00edmica Org\u00e2nica e Inorg\u00e2nica Universidade Federal do Cear\u00e1 Fortaleza Cear\u00e1 Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta S. 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