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Novel strategies are needed to deal with the challenge caused by drug\u2010resistant bacteria. Here, we report a new approach to combat infections by targeting iron\u2010binding proteins to suppress bacterial growth. We investigated the function of the conserved periplasmic binding protein FecB from\n                    <jats:italic>Vibrio alginolyticus<\/jats:italic>\n                    . FecB was known to play a crucial role in the bacterial growth and to relate with biofilm formation. We then solved the crystal structures and elucidated the binding mechanism of FecB with ferric ion chelated by citrate. The results indicated that FecB binds weakly to one citrate molecule and strongly to the Fe\n                    <jats:sup>3+<\/jats:sup>\n                    \u2010(citrate)\n                    <jats:sub>2<\/jats:sub>\n                    complex. Based on these results, a structure\u2010based virtual screening approach was conducted against FecB to identify small molecules that block ferric citrate uptake. Further evaluations\n                    <jats:italic>in vivo<\/jats:italic>\n                    and\n                    <jats:italic>in vitro<\/jats:italic>\n                    demonstrated that salvianolic acid C significantly suppressed bacterial growth, indicating that targeting bacterial nutrient absorption is a promising strategy for identifying potential antibacterial drugs.\n                  <\/jats:p>","DOI":"10.1002\/anie.202411688","type":"journal-article","created":{"date-parts":[[2024,9,20]],"date-time":"2024-09-20T23:24:44Z","timestamp":1726874684000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Structure\u2010Guided Discovery of a Potent Inhibitor of the Ferric Citrate Binding Protein FecB in\n                    <i>Vibrio<\/i>\n                    Bacteria"],"prefix":"10.1002","volume":"63","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6963-7200","authenticated-orcid":false,"given":"Jinyan","family":"Jiang","sequence":"first","affiliation":[{"name":"Department of Applied Biological Chemistry Graduate School of Agricultural and Life Science The University of Tokyo  1-1-1 Yayoi, Bunkyo-ku Tokyo 113-8657 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9184-5601","authenticated-orcid":false,"given":"Suguru","family":"Okuda","sequence":"additional","affiliation":[{"name":"Department of Applied Biological Chemistry Graduate School of Agricultural and Life Science The University of Tokyo  1-1-1 Yayoi, Bunkyo-ku Tokyo 113-8657 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6590-6976","authenticated-orcid":false,"given":"Hideaki","family":"Itoh","sequence":"additional","affiliation":[{"name":"Department of Applied Biological Chemistry Graduate School of Agricultural and Life Science The University of Tokyo  1-1-1 Yayoi, Bunkyo-ku Tokyo 113-8657 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2760-5344","authenticated-orcid":false,"given":"Ken","family":"Okamoto","sequence":"additional","affiliation":[{"name":"Department of Applied Biological Chemistry Graduate School of Agricultural and Life Science The University of Tokyo  1-1-1 Yayoi, Bunkyo-ku Tokyo 113-8657 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5556-5058","authenticated-orcid":false,"given":"Hiromi","family":"Nakanishi","sequence":"additional","affiliation":[{"name":"Department of Global Agricultural Sciences Graduate School of Agricultural and Life Science The University of Tokyo  1-1-1 Yayoi Bunkyo-ku Tokyo 113-8657 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