5JLD

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

Summary for 5JLD

• Entry DOI: 10.2210/pdb5jld/pdb
• Descriptor: Arginyl-tRNA synthetase, putative (2 entities in total)
• Functional Keywords: arginyl-trna synthetase, translation, malaria, ligase
• Biological source: Plasmodium falciparum (isolate 3D7)
• Total number of polymer chains: 1
• Total formula weight: 69515.46

Authors

Jain, V.,Manickam, Y.,Sharma, A. (deposition date: 2016-04-27, release date: 2016-08-24, Last modification date: 2023-11-08)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.2 Å)