E166在临床β-内酰胺酶抑制剂舒巴坦的亚胺向烯胺互变异构中的作用。
Role of E166 in the imine to enamine tautomerization of the clinical beta-lactamase inhibitor sulbactam.
作者信息
Kalp Matthew, Buynak John D, Carey Paul R
机构信息
Department of Biochemistry, School of Medicine, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, Ohio 44106, USA.
出版信息
Biochemistry. 2009 Nov 3;48(43):10196-8. doi: 10.1021/bi901416t.
Abstract
Mechanism-based inhibitors of class A beta-lactamases, such as sulbactam, undergo a complex series of chemical reactions in the enzyme active site. Formation of a trans-enamine acyl-enzyme via a hydrolysis-prone imine is responsible for transient inhibition of the enzyme. Although the imine to enamine tautomerization is crucial to inhibition of the enzyme, there are no experimental data to suggest how this chemical transformation is catalyzed in the active site. In this report, we show that E166 acts as a general base to promote the imine to enamine tautomerization.
摘要
A类β-内酰胺酶的基于机制的抑制剂，如舒巴坦，在酶活性位点会经历一系列复杂的化学反应。通过易于水解的亚胺形成反式烯胺酰基酶负责对酶的瞬时抑制。虽然亚胺到烯胺的互变异构对于酶的抑制至关重要，但尚无实验数据表明这种化学转化在活性位点是如何被催化的。在本报告中，我们表明E166作为一个通用碱促进亚胺到烯胺的互变异构。
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Different intermediate populations formed by tazobactam, sulbactam, and clavulanate reacting with SHV-1 beta-lactamases: Raman crystallographic evidence.他唑巴坦、舒巴坦和克拉维酸与SHV-1β-内酰胺酶反应形成的不同中间产物群体：拉曼晶体学证据。
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