Department of Pharmaceutical Sciences, Western University of Health Sciences, Pomona, CA, USA.
Antimicrob Agents Chemother. 2012 Dec;56(12):6403-6. doi: 10.1128/AAC.01440-12. Epub 2012 Sep 24.
Metallo-β-lactamases are important determinants of antibacterial resistance. In this study, we investigate the sequence-activity relationship between the closely related enzymes IMP-1, IMP-6, and IMP-25. While IMP-1 is the more efficient enzyme across the overall spectrum of tested β-lactam antibacterial agents, IMP-6 and IMP-25 seem to have evolved to specifically inactivate the newer carbapenem meropenem. Molecular modeling indicates that the G235S mutation distinguishing IMP-25 from IMP-1 and IMP-6 may affect enzyme activity via Asn233.
金属β-内酰胺酶是抗菌耐药性的重要决定因素。在这项研究中，我们研究了密切相关的酶 IMP-1、IMP-6 和 IMP-25 之间的序列-活性关系。虽然 IMP-1 是在整个测试的β-内酰胺类抗菌药物的广谱范围内更有效的酶，但 IMP-6 和 IMP-25 似乎已经进化为专门失活新型碳青霉烯类美罗培南。分子建模表明，将 IMP-25 与 IMP-1 和 IMP-6 区分开来的 G235S 突变可能通过 Asn233 影响酶活性。
