4TWA

Crystal Structure of Prolyl-tRNA Synthetase (PRS) from Plasmodium falciparum

4TWA の概要

• エントリーDOI: 10.2210/pdb4twa/pdb
• 分子名称: Proline--tRNA ligase, CHLORIDE ION, SULFATE ION, ... (4 entities in total)
• 機能のキーワード: protein translation, halofuginone, malaria, inhibitor, prs, synthetase, ligase
• 由来する生物種: Plasmodium falciparum
• 細胞内の位置: Cytoplasm : Q8I5R7
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 116871.79

構造登録者

Jain, V.,Yogavel, M.,Sharma, A. (登録日: 2014-06-30, 公開日: 2014-08-13, 最終更新日: 2023-09-27)

主引用文献

Jain, V.,Kikuchi, H.,Oshima, Y.,Sharma, A.,Yogavel, M.
Structural and functional analysis of the anti-malarial drug target prolyl-tRNA synthetase.
J. Struct. Funct. Genomics, 15:181-190, 2014

PubMed Abstract: Aminoacyl-tRNA synthetases (aaRSs) drive protein translation in cells and hence these are essential enzymes across life. Inhibition of these enzymes can halt growth of an organism by stalling protein translation. Therefore, small molecule targeting of aaRS active sites is an attractive avenue from the perspective of developing anti-infectives. Febrifugine and its derivatives like halofuginone (HF) are known to inhibit prolyl-tRNA synthetase of malaria parasite Plasmodium falciparum. Here, we present functional and crystallographic data on P. falciparum prolyl-tRNA synthetase (PfPRS). Using immunofluorescence data, we show that PfPRS is exclusively resident in the parasite cytoplasm within asexual blood stage parasites. The inhibitor HF interacts strongly with PfPRS in a non-competitive binding mode in presence or absence of ATP analog. Intriguingly, the two monomers that constitute dimeric PfPRS display significantly different conformations in their active site regions. The structural analyses presented here provide a framework for development of febrifugine derivatives that can seed development of new anti-malarials.

PubMed: 25047712
DOI: 10.1007/s10969-014-9186-x

実験手法

X-RAY DIFFRACTION (3 Å)