Aminoacyl-tRNA synthetases (aaRSs) are essential enzymes in protein translation machinery that provide the charged tRNAs needed for protein synthesis. Over the past decades, aaRSs have been studied as anti-parasitic, anti-bacterial, and anti-fungal drug targets. This study focused on the cytoplasmic glutamyl-tRNA synthetase (GluRS) from Plasmodium falciparum, which belongs to class Ib in aaRSs. GluRS unlike most other aaRSs requires tRNA to activate its cognate amino acid substrate L-Glutamate (L-Glu), and fails to form an intermediate adenylate complex in the absence of tRNA. The crystal structures of the Apo, ATP, and ADP-bound forms of Plasmodium falciparum glutamyl-tRNA synthetase (PfGluRS) were solved at 2.1 Å, 2.2 Å, and 2.8 Å respectively. The structural comparison of the Apo- and ATP-bound holo-forms of PfGluRS showed considerable conformational changes in the loop regions around the ATP-binding pocket of the enzyme. Biophysical characterization of the PfGluRS showed binding of the enzyme substrates L-Gluand ATP.. The sequence and structural conservation were evident across GluRS compared to other species. The structural dissection of the PfGluRS gives insight into the critical residues involved in the binding of ATP substrate, which can be harvested to develop new antimalarial drugs.

氨酰-tRNA 合成酶 (aaRS) 是蛋白质翻译机制中必不可少的酶，可提供蛋白质合成所需的带电 tRNA。在过去的几十年中，aaRS 已作为抗寄生虫、抗细菌和抗真菌药物靶标进行了研究。本研究的重点是来自恶性疟原虫的细胞质谷氨酰-tRNA 合成酶 (GluRS) ，它属于 aaRS 中的 Ib 类。与大多数其他 aaRS 不同，GluRS 需要 tRNA 来激活其同源氨基酸底物L-谷氨酸 ( L -Glu)，并且在没有 tRNA 的情况下无法形成中间腺苷酸复合物。Apo、ATP 和 ADP 结合形式的恶性疟原虫谷氨酰-tRNA 合成酶的晶体结构（PfGluRS) 分别在 2.1 Å、2.2 Å 和 2.8 Å 处解析。Pf GluRS的 Apo 和 ATP 结合的全息形式的结构比较表明，酶的 ATP 结合口袋周围的环区域发生了相当大的构象变化。Pf GluRS的生物物理表征显示酶底物L -Glu 和 ATP 的结合。与其他物种相比，GluRS 的序列和结构保守性很明显。Pf GluRS的结构剖析可以深入了解参与 ATP 底物结合的关键残基，这些残基可以用来开发新的抗疟药。