Crystal structures of Toxoplasma gondii HGXPRTase reveal the catalytic role of a long flexible loop
Crystal structures of Toxoplasma gondii HGXPRTase reveal the catalytic role of a long flexible loop
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弓形虫HGXPRTase的晶体结构揭示了长柔性环的催化作用
DOI：
10.1038/nsb1096-881
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发表时间：
1996
期刊：
影响因子：
--
通讯作者：
R. Brennan
中科院分区：
文献类型：
--
作者：
M. Schumacher;D. Carter;D. Roos;B. Ullman;R. Brennan
条件致病弓形虫次黄嘌呤-鸟嘌呤-黄嘌呤磷酸核糖基转移酶(HGXPRTase)的晶体结构分别达到2.4和2.9？分辨率。HGXPRTase显示保守的PRTase折叠。在与其产物结合的酶的结构中，一个长的柔性环(残基115-126)位于远离活性部位的位置。与无底物结构的比较表明，环发生了显著的重新定位，准备覆盖催化口袋，从而提供了一种机制，通过这种机制，HG(X)PRTase保护它们的氧碳正离子过渡态免受本体溶剂的亲核攻击。环中保守的Ser117-Tyr118二肽被带到活性部位，完成了催化残基的集成。
Crystal structures of substrate-free and XMP-soaked hypoxanthine-guanine-xanthine phosphoribosyltransferase (HGXPRTase) of the opportunistic pathogenToxoplasma gondiihave been determined to 2.4 and 2.9 Å resolution, respectively. HGXPRTase displays the conserved PRTase fold. In the structure of the enzyme bound to its product, a long flexible loop (residues 115–126) is located away from the active site. Comparison to the substrate-free structure reveals a striking relocation of the loop, which is poised to cover the catalytic pocket, thus providing a mechanism by which the HG(X)PRTases shield their oxocarbonium transition states from nucleophilic attack by the bulk solvent. The conserved Ser 117-Tyr 118 dipeptide within the loop is brought to the active site, completing the ensemble of catalytic residues.