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FosB is a fosfomycin resistance enzyme found in Gram\u2010positive pathogens like\n                    <jats:italic>E. faecium<\/jats:italic>\n                    . Typically, the FosB enzymes are Mn\n                    <jats:sup>2+<\/jats:sup>\n                    \u2010dependent bacillithiol (BSH) transferases that inactivate fosfomycin through nucleophilic addition of the thiol to the antibiotic. However, our kinetic analysis of FosB\n                    <jats:sup>\n                      <jats:italic>Ef<\/jats:italic>\n                    <\/jats:sup>\n                    shows that the enzyme does not utilize BSH as a thiol substrate, unlike the other well characterized FosB enzymes. Here we report that FosB\n                    <jats:sup>\n                      <jats:italic>Ef<\/jats:italic>\n                    <\/jats:sup>\n                    is a Mn\n                    <jats:sup>2+<\/jats:sup>\n                    \u2010dependent\n                    <jats:italic>L<\/jats:italic>\n                    \u2010cys transferase. In addition, we have determined the three\u2010dimensional X\u2010ray crystal structure of FosB\n                    <jats:sup>\n                      <jats:italic>Ef<\/jats:italic>\n                    <\/jats:sup>\n                    in complex with fosfomycin at a resolution of 2.0\u00a0\u00c5. A sequence similarity network (SSN) was generated for the FosB family to investigate the unexpected substrate selectivity. Three non\u2010conserved residues were identified in the SSN that may contribute to the substrate selectivity differences in the family of enzymes. Our structural and functional characterization of FosB\n                    <jats:sup>\n                      <jats:italic>Ef<\/jats:italic>\n                    <\/jats:sup>\n                    establishes the enzyme as a potential target and may prove useful for future structure\u2010based development of FosB inhibitors to increase the efficacy of fosfomycin.\n                  <\/jats:p>","DOI":"10.1002\/pro.4253","type":"journal-article","created":{"date-parts":[[2021,12,9]],"date-time":"2021-12-09T09:44:37Z","timestamp":1639043077000},"page":"580-590","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Structural and functional characterization of fosfomycin resistance conferred by\n                    <scp>FosB<\/scp>\n                    from\n                    <scp>\n                      <i>Enterococcus faecium<\/i>\n                    <\/scp>"],"prefix":"10.1002","volume":"31","author":[{"given":"Vanessa","family":"Wiltsie","sequence":"first","affiliation":[{"name":"Department of Chemistry &amp; Biochemistry The University of Alabama  Tuscaloosa Alabama USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Skye","family":"Travis","sequence":"additional","affiliation":[{"name":"Department of Chemistry &amp; Biochemistry The University of Alabama  Tuscaloosa Alabama USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madeline R.","family":"Shay","sequence":"additional","affiliation":[{"name":"Department of Chemistry &amp; Biochemistry The University of Alabama  Tuscaloosa Alabama USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zachary","family":"Simmons","sequence":"additional","affiliation":[{"name":"Department of Chemistry &amp; Biochemistry The University of Alabama  Tuscaloosa Alabama USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Frantom","sequence":"additional","affiliation":[{"name":"Department of Chemistry &amp; Biochemistry The University of Alabama  Tuscaloosa Alabama USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1964-3896","authenticated-orcid":false,"given":"Matthew K.","family":"Thompson","sequence":"additional","affiliation":[{"name":"Department of Chemistry &amp; Biochemistry The University of Alabama  Tuscaloosa Alabama USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,12,22]]},"reference":[{"key":"e_1_2_9_2_1","unstructured":"Infographic.Antibiotic resistance the global threat. 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