肺炎克雷伯菌碳青霉烯酶（KPC-2）底物识别与产物释放的分子基础
Molecular Basis of Substrate Recognition and Product Release by the Klebsiella pneumoniae Carbapenemase (KPC-2).
作者信息
Pemberton Orville A, Zhang Xiujun, Chen Yu
机构信息
Department of Molecular Medicine, University of South Florida , 12901 Bruce B. Downs Boulevard, Tampa, Florida 33612, United States.
出版信息
J Med Chem. 2017 Apr 27;60(8):3525-3530. doi: 10.1021/acs.jmedchem.7b00158. Epub 2017 Apr 17.
Abstract
Carbapenem-resistant Enterobacteriaceae are resistant to most β-lactam antibiotics due to the production of the Klebsiella pneumoniae carbapenemase (KPC-2) class A β-lactamase. Here, we present the first product complex crystal structures of KPC-2 with β-lactam antibiotics containing hydrolyzed cefotaxime and faropenem. They provide experimental insights into substrate recognition by KPC-2 and its unique cephalosporinase/carbapenemase activity. These structures also represent the first product complexes for a wild-type serine β-lactamase, elucidating the product release mechanism of these enzymes in general.
摘要
耐碳青霉烯类肠杆菌科细菌由于产生肺炎克雷伯菌碳青霉烯酶（KPC-2）A类β-内酰胺酶而对大多数β-内酰胺类抗生素耐药。在此，我们展示了KPC-2与含有水解头孢噻肟和法罗培南的β-内酰胺类抗生素的首个产物复合物晶体结构。它们为KPC-2的底物识别及其独特的头孢菌素酶/碳青霉烯酶活性提供了实验见解。这些结构也代表了野生型丝氨酸β-内酰胺酶的首个产物复合物，总体上阐明了这些酶的产物释放机制。
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