Structure of Bacillus subtilis γ-glutamyltranspeptidase in complex with acivicin: diversity of the binding mode of a classical and electrophilic active-site-directed glutamate analogue.
Structure of Bacillus subtilis γ-glutamyltranspeptidase in complex with acivicin: diversity of the binding mode of a classical and electrophilic active-site-directed glutamate analogue.
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DOI：
10.1107/s1399004713031222
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发表时间：
2014-02
期刊：
影响因子：
--
通讯作者：
Wada K
中科院分区：
文献类型：
--
作者：
Ida T;Suzuki H;Fukuyama K;Hiratake J;Wada K
acivicin是一种经典的亲电活性位点谷氨酸类似物，与细菌γ-谷氨酰转肽酶的结合方式多种多样。γ-谷氨酰转肽酶（GGT）是一种在谷胱甘肽代谢中起核心作用的酶，而阿西维辛是GGT的经典抑制剂。在这里，结合枯草芽孢杆菌GGT的阿西维辛的结构，通过X-射线晶体学确定的1.8 μ m分辨率，其中它结合的活性位点以类似的方式在幽门螺杆菌GGT，但在一个不同的结合模式，在大肠杆菌GGT。 在B。在枯草杆菌GGT中，acivicin通过其C3原子以sp 2杂交共价结合至酶的催化亲核试剂Thr 403 Oγ。 结果表明，在谷氨酰转肽酶的结合口袋中，阿西维辛的结合位点是常见的，但其五元二氢异恶唑环的结合方式和方向是多样的。
The binding modes of acivicin, a classical and an electrophilic active-site-directed glutamate analogue, to bacterial γ-glutamyltranspeptidases were found to be diverse. γ-Glutamyltranspeptidase (GGT) is an enzyme that plays a central role in glutathione metabolism, and acivicin is a classical inhibitor of GGT. Here, the structure of acivicin bound to Bacillus subtilis GGT determined by X-ray crystallography to 1.8 Å resolution is presented, in which it binds to the active site in a similar manner to that in Helicobacter pylori GGT, but in a different binding mode to that in Escherichia coli GGT. In B. subtilis GGT, acivicin is bound covalently through its C3 atom with sp 2 hybridization to Thr403 Oγ, the catalytic nucleophile of the enzyme. The results show that acivicin-binding sites are common, but the binding manners and orientations of its five-membered dihydroisoxazole ring are diverse in the binding pockets of GGTs.