4PG3

Crystal structure of KRS complexed with inhibitor

4PG3 の概要

• エントリーDOI: 10.2210/pdb4pg3/pdb
• 分子名称: Lysine--tRNA ligase, LYSINE, cladosporin, ... (4 entities in total)
• 機能のキーワード: inhibitor, krs, complex, ligase-ligase inhibitor complex, ligase/ligase inhibitor
• 由来する生物種: Plasmodium falciparum
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 236585.82

構造登録者

Sharma, A.,Yogavel, M.,Khan, S.,Sharma, A.,Belrhali, H. (登録日: 2014-05-01, 公開日: 2014-07-16, 最終更新日: 2024-11-20)

主引用文献

Khan, S.,Sharma, A.,Belrhali, H.,Yogavel, M.,Sharma, A.
Structural basis of malaria parasite lysyl-tRNA synthetase inhibition by cladosporin.
J. Struct. Funct. Genomics, 15:63-71, 2014

PubMed Abstract: Malaria parasites inevitably develop drug resistance to anti-malarials over time. Hence the immediacy for discovering new chemical scaffolds to include in combination malaria drug therapy. The desirable attributes of new chemotherapeutic agents currently include activity against both liver and blood stage malaria parasites. One such recently discovered compound called cladosporin abrogates parasite growth via inhibition of Plasmodium falciparum lysyl-tRNA synthetase (PfKRS), an enzyme central to protein translation. Here, we present crystal structure of ternary PfKRS-lysine-cladosporin (PfKRS-K-C) complex that reveals cladosporin's remarkable ability to mimic the natural substrate adenosine and thereby colonize PfKRS active site. The isocoumarin fragment of cladosporin sandwiches between critical adenine-recognizing residues while its pyran ring fits snugly in the ribose-recognizing cavity. PfKRS-K-C structure highlights ample space within PfKRS active site for further chemical derivatization of cladosporin. Such derivatives may be useful against additional human pathogens that retain high conservation in cladosporin chelating residues within their lysyl-tRNA synthetase.

PubMed: 24935905
DOI: 10.1007/s10969-014-9182-1

実験手法

X-RAY DIFFRACTION (2.696 Å)