5HGQ

Loa loa Lysyl-tRNA synthetase in complex with Cladosporin.

5HGQ の概要

• エントリーDOI: 10.2210/pdb5hgq/pdb
• 分子名称: Lysine--tRNA ligase, LYSINE, cladosporin, ... (5 entities in total)
• 機能のキーワード: cladosporin, lysine-trna synthetase, loa loa, helminth parasites, ligase-ligase inhibitor complex, ligase/ligase inhibitor
• 由来する生物種: Loa loa (Eye worm)
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 242159.13

構造登録者

Sharma, A.,Sharma, M.,Yogavel, M.,Sharma, A. (登録日: 2016-01-08, 公開日: 2016-10-26, 最終更新日: 2023-11-08)

主引用文献

Sharma, A.,Sharma, M.,Yogavel, M.,Sharma, A.
Protein Translation Enzyme lysyl-tRNA Synthetase Presents a New Target for Drug Development against Causative Agents of Loiasis and Schistosomiasis
PLoS Negl Trop Dis, 10:e0005084-e0005084, 2016

PubMed Abstract: Helminth parasites are an assemblage of two major phyla of nematodes (also known as roundworms) and platyhelminths (also called flatworms). These parasites are a major human health burden, and infections caused by helminths are considered under neglected tropical diseases (NTDs). These infections are typified by limited clinical treatment options and threat of drug resistance. Aminoacyl-tRNA synthetases (aaRSs) are vital enzymes that decode genetic information and enable protein translation. The specific inhibition of pathogen aaRSs bores well for development of next generation anti-parasitics. Here, we have identified and annotated aaRSs and accessory proteins from Loa loa (nematode) and Schistosoma mansoni (flatworm) to provide a glimpse of these protein translation enzymes within these parasites. Using purified parasitic lysyl-tRNA synthetases (KRSs), we developed series of assays that address KRS enzymatic activity, oligomeric states, crystal structure and inhibition profiles. We show that L. loa and S. mansoni KRSs are potently inhibited by the fungal metabolite cladosporin. Our co-crystal structure of Loa loa KRS-cladosporin complex reveals key interacting residues and provides a platform for structure-based drug development. This work hence provides a new direction for both novel target discovery and inhibitor development against eukaryotic pathogens that include L. loa and S. mansoni.

PubMed: 27806050
DOI: 10.1371/journal.pntd.0005084

実験手法

X-RAY DIFFRACTION (3.283 Å)