College of Life Sciences, Nankai University, Tianjin, 30071, China.
College of Life Sciences, Nankai University, Tianjin, 30071, China.
Biochem Biophys Res Commun. 2019 Mar 5;510(2):224-229. doi: 10.1016/j.bbrc.2019.01.069. Epub 2019 Jan 28.
Organophosphates (OPs) have been used widely as insecticides for protecting the agricultural crops from the pests. These compounds are highly toxic because they can cause the irreversible damage to human nervous system. Phosphotriesterases (PTEs), widely exist in many different kinds of bacteria, insects and mammals, can hydrolyze phosphotriesters (one major kind of OP) sufficiently. The phosphotriesterase-activities of PTEs are considered to derive from the lactonase-activities during the evolution, and phosphotriesterase-like lactonase family (PLL), is the closest protein family to PTE family based on protein-protein blast results. But members of PLL family exhibit higher lactonase activities than the phosphotriesterase activities, while the best substrates for PTEs are phosphotriesters. In this paper, the X-ray crystal structure of phosphotriesterase from M. tuberculosis (mPHP) was solved at a resolution of 2.3 Å. The structure reveals that the mPHP is a dimer with a typical distorted (β/α) barrel structure like other structures of PLL family and PTE family. The architecture of active pocket of mPHP coordinates with 2 metal ions which is also similar to other PLLs and PTEs. The activity assay proved the mPHP is biological active form and the Atomic Absorption Spectroscopy assay gave the evidence that the two metal ions bound to the active pocket were Zinc cations. The structural comparison between mPHP and other homologues concluded that the mPHP should belong to PLL family, not PTE family.
有机磷化合物（OPs）被广泛用作杀虫剂，以保护农作物免受害虫侵害。这些化合物毒性很高，因为它们会对人体神经系统造成不可逆转的损害。磷酸三酯酶（PTEs）广泛存在于许多不同种类的细菌、昆虫和哺乳动物中，可以充分水解磷酸三酯（OP 的主要种类之一）。PTEs 的磷酸三酯酶活性被认为是在进化过程中从内酯酶活性中衍生而来的，而磷酸三酯酶样内酯酶家族（PLL）是基于蛋白质-蛋白质 Blast 结果与 PTE 家族最接近的蛋白质家族。但是，PLL 家族的成员表现出比磷酸三酯酶活性更高的内酯酶活性，而 PTEs 的最佳底物是磷酸三酯。在本文中，我们解决了结核分枝杆菌（mPHP）的磷酸三酯酶的 X 射线晶体结构，分辨率为 2.3 Å。该结构表明，mPHP 是一个二聚体，具有典型的扭曲（β/α）桶结构，类似于其他 PLL 家族和 PTE 家族的结构。mPHP 的活性口袋的结构与 2 个金属离子配位，这也与其他 PLL 和 PTE 相似。活性测定证明 mPHP 是具有生物活性的形式，原子吸收光谱测定给出了结合到活性口袋的两个金属离子是锌离子的证据。mPHP 与其他同源物的结构比较表明，mPHP 应该属于 PLL 家族，而不是 PTE 家族。
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