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For example, in 2022 tuberculosis (TB) was the second leading infectious killer after COVID-19, with\u00a0multi-drug-resistant strains of TB having an \u223c40% fatality rate. Targeting essential biosynthetic pathways in pathogens has proven to be successful for the development of novel antimicrobial treatments. Fatty-acid synthesis (FAS) in bacteria proceeds via the type II pathway, which is substantially different from the type I pathway utilized in animals. This makes bacterial fatty-acid biosynthesis (Fab) enzymes appealing as drug targets. FabG is an essential FASII enzyme, and some bacteria, such as\n                    <jats:italic>Mycobacterium tuberculosis<\/jats:italic>\n                    , the causative agent of TB, harbor multiple homologs. FabG4 is a conserved, high-molecular-weight FabG (HMwFabG) that was first identified in\n                    <jats:italic>M. tuberculosis<\/jats:italic>\n                    and is distinct from the canonical low-molecular-weight FabG. Here, structural and functional analyses of\n                    <jats:italic>Mycolicibacterium smegmatis<\/jats:italic>\n                    FabG4, the third HMwFabG studied to date, are reported. Crystal structures of NAD\n                    <jats:sup>+<\/jats:sup>\n                    and apo\n                    <jats:italic>Ms<\/jats:italic>\n                    FabG4, along with kinetic analyses, show that\n                    <jats:italic>Ms<\/jats:italic>\n                    FabG4 preferentially binds and uses NADH when reducing CoA substrates. As\n                    <jats:italic>M. smegmatis<\/jats:italic>\n                    is often used as a model organism for\n                    <jats:italic>M. tuberculosis<\/jats:italic>\n                    , these studies may aid the development of drugs to treat TB and add to the growing body of research that distinguish HMwFabGs from the archetypal low-molecular-weight FabG.\n                  <\/jats:p>","DOI":"10.1107\/s2053230x2400356x","type":"journal-article","created":{"date-parts":[[2024,4,24]],"date-time":"2024-04-24T11:03:38Z","timestamp":1713956618000},"page":"82-91","update-policy":"https:\/\/doi.org\/10.1107\/cm_01","source":"Crossref","is-referenced-by-count":3,"title":["Structural and functional characterization of FabG4 from\n                    <i>Mycolicibacterium smegmatis<\/i>"],"prefix":"10.1107","volume":"80","author":[{"given":"Xinping","family":"Ran","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/022x6qg61","id-type":"ROR","asserted-by":"publisher"}],"department":["Department of Chemistry"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Prashit","family":"Parikh","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/022x6qg61","id-type":"ROR","asserted-by":"publisher"}],"department":["Department of Chemistry"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8229-3243","authenticated-orcid":true,"given":"Jan","family":"Abendroth","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tracy L.","family":"Arakaki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew C.","family":"Clifton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0474-8003","authenticated-orcid":true,"given":"Thomas E.","family":"Edwards","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9638-8083","authenticated-orcid":true,"given":"Donald D.","family":"Lorimer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen","family":"Mayclin","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/028qka468","id-type":"ROR","asserted-by":"publisher"}]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9570-5086","authenticated-orcid":true,"given":"Bart L.","family":"Staker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0056-0513","authenticated-orcid":true,"given":"Peter","family":"Myler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4105-1042","authenticated-orcid":true,"given":"Krystle J.","family":"McLaughlin","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/022x6qg61","id-type":"ROR","asserted-by":"publisher"}],"department":["Department of Chemistry"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"329","published-online":{"date-parts":[[2024,4,24]]},"reference":[{"key":"ir5029_bb1","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1107\/S2059798323003595","volume":"79","author":"Agirre","year":"2023","journal-title":"Acta Cryst. 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