5JLD

Crystal Structure of Arginyl-tRNA Synthetase from Plasmodium falciparum (PfRRS)

5JLD の概要

• エントリーDOI: 10.2210/pdb5jld/pdb
• 分子名称: Arginyl-tRNA synthetase, putative (2 entities in total)
• 機能のキーワード: arginyl-trna synthetase, translation, malaria, ligase
• 由来する生物種: Plasmodium falciparum (isolate 3D7)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 69515.46

構造登録者

Jain, V.,Manickam, Y.,Sharma, A. (登録日: 2016-04-27, 公開日: 2016-08-24, 最終更新日: 2023-11-08)

主引用文献

Jain, V.,Yogavel, M.,Sharma, A.
Dimerization of Arginyl-tRNA Synthetase by Free Heme Drives Its Inactivation in Plasmodium falciparum
Structure, 24:1476-1487, 2016

PubMed Abstract: Excess cellular heme is toxic, and malaria parasites regulate its levels during hemoglobin digestion. Aminoacyl-tRNA synthetases are ubiquitous enzymes, and of these, arginyl-tRNA synthetase (RRS) is unique as its enzymatic product of charged tRNA is required for protein synthesis and degradation. We show that Plasmodium falciparum arginyl-tRNA synthetase (PfRRS) is an active, cytosolic, and monomeric enzyme. Its high-resolution crystal structure highlights critical structural differences with the human enzyme. We further show that hemin binds to and inhibits the aminoacylation activity of PfRRS. Hemin induces a dimeric form of PfRRS that is thus rendered enzymatically dead as it is unable to recognize its cognate tRNA(arg). Excessive hemin in chloroquine-treated malaria parasites results in significantly reduced charged tRNA(arg) levels, thus suggesting deceleration of protein synthesis. These data together suggest that the inhibition of Plasmodium falciparum arginyl-tRNA synthetase can now be synergized with existing antimalarials for more potent drug cocktails against malaria parasites.

PubMed: 27502052
DOI: 10.1016/j.str.2016.06.018

実験手法

X-RAY DIFFRACTION (2.2 Å)