Binding of (5S)-Penicilloic Acid to Penicillin Binding Protein 3

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• 作者：Sander S. van Berkel ; Joanne E. Nettleship ; Ivanhoe K. H. Leung ; J眉rgen Brem ; Hwanho Choi ; David I. Stuart ; Timothy D. W. Claridge ; Michael A. McDonough ; Raymond J. Owens ; Jingshan Ren ; Christopher J. Schofield
• 刊名：ACS Chemical Biology
• 出版年：2013
• 出版时间：October 18, 2013
• 年：2013
• 卷：8
• 期：10
• 页码：2112-2116
• 全文大小：336K
• 年卷期：v.8,no.10(October 18, 2013)
• ISSN：1554-8937

文摘

尾-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.