Oelschlaeger Peter, Aitha Mahesh, Yang Hao, Kang Joon S, Zhang Antonia L, Liu Eleanor M, Buynak John D, Crowder Michael W
Department of Pharmaceutical Sciences, College of Pharmacy, Western University of Health Sciences, Pomona, California, USA
Department of Chemistry and Biochemistry, Miami University, Oxford, Ohio, USA.
Antimicrob Agents Chemother. 2015 Jul;59(7):4326-30. doi: 10.1128/AAC.04409-14. Epub 2015 Apr 27.
Metallo-β-lactamases inactivate most β-lactam antibacterials, and much attention has been paid to their catalytic mechanism. One issue of controversy has been whether β-lactam hydrolysis generally proceeds through an anionic intermediate bound to the active-site Zn(II) ions or not. The formation of an intermediate has not been shown conclusively in imipenemase (IMP) enzymes to date. Here, we provide evidence that intermediates are formed during the hydrolysis of meropenem and chromacef catalyzed by the variant IMP-25 and, to a lesser degree, IMP-1.
金属β-内酰胺酶可使大多数β-内酰胺类抗菌药物失活，人们对其催化机制给予了高度关注。一个存在争议的问题是，β-内酰胺水解通常是否通过与活性位点锌（II）离子结合的阴离子中间体进行。迄今为止，在亚胺培南酶（IMP）中尚未确凿地证明中间体的形成。在此，我们提供证据表明，在变体IMP-25催化美罗培南和头孢色腙水解的过程中会形成中间体，IMP-1催化时形成中间体的程度较小。
