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Importantly, FGD2 is found only in pathogenic mycobacteria, making it a potential drug target. While some suggest it functions as a glucose\u20106\u2010phosphate dehydrogenase, others propose it acts instead as an F\n                    <jats:sub>420<\/jats:sub>\n                    \u2010dependent hydroxy\u2010mycolic acid dehydrogenase\u2014an activity linked to cell\u2010wall remodeling and inhibition by the anti\u2010tubercular drug pretomanid. Yet, direct evidence for either activity has been lacking. Here, we heterologously express and purify active Mtb\u2010FGD2, and demonstrate that the enzyme binds the F\n                    <jats:sub>420<\/jats:sub>\n                    cofactor with nanomolar affinity. Crystal structures for both the\n                    <jats:italic>apo\u2010<\/jats:italic>\n                    form and the F\n                    <jats:sub>420<\/jats:sub>\n                    complex reveal that the Mtb\u2010FGD2 active site architecture is consistent with sugar substrates but notably lacks a phosphate\u2010binding pocket. Biochemical assays confirm that Mtb\u2010FGD2 functions efficiently as an F\n                    <jats:sub>420<\/jats:sub>\n                    \u2010dependent glucose dehydrogenase in\u00a0vitro. Computational docking combined with molecular dynamics simulations further supports the formation of a catalytically plausible \u03b2\u2010D\u2010glucose:F\n                    <jats:sub>420<\/jats:sub>\n                    ternary complex. When coupled to other F\n                    <jats:sub>420<\/jats:sub>\n                    \u2010dependent enzymes, Mtb\u2010FGD2 readily supports glucose\u2010driven F\n                    <jats:sub>420<\/jats:sub>\n                    .H\n                    <jats:sub>2<\/jats:sub>\n                    \u2010dependent oxidoreductase activity. Our data thus suggest that the Mtb\u2010FGD2 provides reduced F\n                    <jats:sub>420<\/jats:sub>\n                    .H\n                    <jats:sub>2<\/jats:sub>\n                    in a glucose\u2010dependent manner to support mycobacterial F\n                    <jats:sub>420<\/jats:sub>\n                    .H\n                    <jats:sub>2<\/jats:sub>\n                    \u2010dependent oxidoreductases in the cell envelope.\n                  <\/jats:p>","DOI":"10.1002\/prot.70139","type":"journal-article","created":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T12:50:46Z","timestamp":1776775846000},"page":"1610-1627","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The\n                    <scp>\n                      <i>Mycobacterium tuberculosis<\/i>\n                    <\/scp>\n                    Rv0132c Gene Product Mtb\u2010\n                    <scp>FGD2<\/scp>\n                    Can Act as an\n                    <scp>\n                      F\n                      <sub>420<\/sub>\n                    <\/scp>\n                    \u2010Dependent Glucose Dehydrogenase"],"prefix":"10.1002","volume":"94","author":[{"given":"Adewale V.","family":"Aderemi","sequence":"first","affiliation":[{"name":"Manchester Institute of Biotechnology, Department of Chemistry University of Manchester  Manchester UK"},{"name":"Osun State University  Osogbo Osun State Nigeria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew","family":"Snee","sequence":"additional","affiliation":[{"name":"Manchester Institute of Biotechnology, Department of Chemistry University of Manchester  Manchester UK"},{"name":"School of Biological Sciences, Faculty of Biology, Medicine and Health, Michael Smith Building University of Manchester  Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard 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UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Derren J.","family":"Heyes","sequence":"additional","affiliation":[{"name":"Manchester Institute of Biotechnology, Department of Chemistry University of Manchester  Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina","family":"Golovanova","sequence":"additional","affiliation":[{"name":"Manchester Institute of Biotechnology, Department of Chemistry University of Manchester  Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas A.","family":"Jowitt","sequence":"additional","affiliation":[{"name":"School of Biological Sciences, Faculty of Biology, Medicine and Health, Michael Smith Building University of Manchester  Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sam","family":"Hay","sequence":"additional","affiliation":[{"name":"Manchester Institute of Biotechnology, Department of Chemistry University of Manchester  Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew W.","family":"Munro","sequence":"additional","affiliation":[{"name":"Manchester Institute of Biotechnology, Department of Chemistry University of Manchester  Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan P.","family":"Waltho","sequence":"additional","affiliation":[{"name":"Manchester Institute of Biotechnology, Department of Chemistry University of Manchester  Manchester UK"},{"name":"School of Biosciences The University of Sheffield  Sheffield UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Leys","sequence":"additional","affiliation":[{"name":"Manchester Institute of Biotechnology, Department of Chemistry University of Manchester  Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,4,21]]},"reference":[{"key":"e_1_2_11_2_1","unstructured":"World 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