Inhibition of the SHV-1 β-lactamase by sulfones:: Crystallographic observation of two reaction intermediates with tazobactam
Inhibition of the SHV-1 β-lactamase by sulfones:: Crystallographic observation of two reaction intermediates with tazobactam
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DOI：
10.1021/bi0022745
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发表时间：
2001-02-13
期刊：
影响因子：
2.9
通讯作者：
Knox, JR
中科院分区：
文献类型：
--
作者：
Kuzin, AP;Nukaga, M;Knox, JR
由SHV-1 A类β -内酰胺酶与砜抑制剂他唑巴坦反应产生的两种物质在100 K下被捕获，并在2.0埃分辨率下通过x射线晶体学绘制。他唑巴坦的无环形式与催化的Ser70侧链共价结合，第二种物质，他唑巴坦的五原子乙烯基羧酸片段，与Ser130结合。提出晶体的电子密度图是两个配合物的复合图，每个配合物只有一个束缚态。据估计，这两种配合物在晶体中以大约相等的数量存在。结果讨论了类似抑制剂舒巴坦和克拉维酸对A类β -内酰胺酶的抑制机制。
Two species resulting from the reaction of the SHV-1 class A beta -lactamase with the sulfone inhibitor tazobactam have been trapped at 100 K and mapped by X-ray crystallography at 2.0 Angstrom resolution. An acyclic form of tazobactam is covalently bonded to the catalytic Ser70 side chain, and a second species, a five-atom vinyl carboxylic acid fragment of tazobactam, is bonded to Ser130. It is proposed that the electron density map of the crystal is a composite picture of two complexes, each with only a single bound species. It is estimated that the two complexes exist in the crystal in approximately equal populations. Results are discussed in relation to the mechanism-based inhibition of class A beta -lactamases by the similar inhibitors sulbactam and clavulanic acid.