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We applied a structural biology approach to characterize a Mip from\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Burkholderia pseudomallei<\/jats:named-content>\n            (BpML1), the causative agent of melioidosis. Crystal structure and nuclear magnetic resonance analyses of BpML1 in complex with known macrocyclics and other derivatives led to the identification of a key chemical scaffold. This scaffold possesses inhibitory potency for BpML1 without the immunosuppressive components of related macrocyclic agents. Biophysical characterization of a compound series with this scaffold allowed binding site specificity in solution and potency determinations for rank ordering the set. The best compounds in this series possessed a low-micromolar affinity for BpML1, bound at the site of enzymatic activity, and inhibited a panel of homologous Mip proteins from other pathogenic bacteria, without demonstrating toxicity in human macrophages. Importantly, the\n            <jats:italic>in vitro<\/jats:italic>\n            activity of BpML1 was reduced by these compounds, leading to decreased macrophage infectivity and intracellular growth of\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Burkholderia pseudomallei<\/jats:named-content>\n            . These compounds offer the potential for activity against a new class of antimicrobial targets and present the utility of a structure-based approach for novel antimicrobial drug discovery.\n          <\/jats:p>","DOI":"10.1128\/aac.01875-13","type":"journal-article","created":{"date-parts":[[2013,12,24]],"date-time":"2013-12-24T04:23:33Z","timestamp":1387859013000},"page":"1458-1467","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":19,"title":["A Structural Biology Approach Enables the Development of Antimicrobials Targeting Bacterial Immunophilins"],"prefix":"10.1128","volume":"58","author":[{"given":"Darren W.","family":"Begley","sequence":"first","affiliation":[{"name":"Emerald Bio, Bainbridge Island, Washington, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"suffix":"III","given":"David","family":"Fox","sequence":"additional","affiliation":[{"name":"Emerald Bio, Bainbridge Island, Washington, 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