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The \u03b2\u2010ketoacyl\u2010ACP synthases carry out the initial elongation reaction of this pathway, utilizing acetyl\u2010CoA as a primer to elongate malonyl\u2010ACP by two carbons, and subsequent elongation of the fatty acyl\u2010ACP substrate by two carbons. Here we describe the structures of the \u03b2\u2010ketoacyl\u2010ACP synthase I from <jats:italic>Brucella melitensis<\/jats:italic> in complex with platencin, 7\u2010hydroxycoumarin, and (5\u2010thiophen\u20102\u2010ylisoxazol\u20103\u2010yl)methanol. The enzyme is a dimer and based on structural and sequence conservation, harbors the same active site configuration as other \u03b2\u2010ketoacyl\u2010ACP synthases. The platencin binding site overlaps with the fatty acyl compound supplied by ACP, while 7\u2010hydroxyl\u2010coumarin and (5\u2010thiophen\u20102\u2010ylisoxazol\u20103\u2010yl)methanol bind at the secondary fatty acyl binding site. These high\u2010resolution structures, ranging between 1.25 and 1.70\u2009\u00e5 resolution, provide a basis for in silico inhibitor screening and optimization, and can aid in rational drug design by revealing the high\u2010resolution binding interfaces of molecules at the malonyl\u2010ACP and acyl\u2010ACP active sites.<\/jats:p>","DOI":"10.1002\/prot.25765","type":"journal-article","created":{"date-parts":[[2019,6,25]],"date-time":"2019-06-25T21:32:41Z","timestamp":1561498361000},"page":"47-56","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Structural characterization of \u03b2\u2010ketoacyl ACP synthase I bound to platencin and fragment screening molecules at two substrate binding sites"],"prefix":"10.1002","volume":"88","author":[{"given":"Edward I.","family":"Patterson","sequence":"first","affiliation":[{"name":"Department of Pathology University of Texas Medical Branch  Galveston 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