Chemistry Research Laboratory, University of Oxford , 12 Mansfield Road, Oxford OX1 3TA, U.K.
ACS Chem Biol. 2013 Oct 18;8(10):2112-6. doi: 10.1021/cb400200h. Epub 2013 Aug 15.
β-Lactam antibiotics react with penicillin binding proteins (PBPs) to form relatively stable acyl-enzyme complexes. We describe structures derived from the reaction of piperacillin with PBP3 (Pseudomonas aeruginosa) including not only the anticipated acyl-enzyme complex but also an unprecedented complex with (5S)-penicilloic acid, which was formed by C-5 epimerization of the nascent (5R)-penicilloic acid product. Formation of the complex was confirmed by solution studies, including NMR. Together, these results will be useful in the design of new PBP inhibitors and raise the possibility that noncovalent PBP inhibition by penicilloic acids may be of clinical relevance.
β-内酰胺类抗生素与青霉素结合蛋白（PBPs）反应形成相对稳定的酰-酶复合物。我们描述了哌拉西林与 PBP3（铜绿假单胞菌）反应生成的结构，包括不仅预期的酰-酶复合物，还有一个前所未有的（5S）-青霉素酸复合物，它是由新生的（5R）-青霉素酸产物的 C-5 差向异构化形成的。通过包括 NMR 在内的溶液研究证实了复合物的形成。这些结果将有助于设计新的 PBP 抑制剂，并提出青霉素酸非共价抑制 PBP 可能具有临床相关性的可能性。
