6LDK

Isoleucyl-tRNA synthetase from Candida albicans complexed with a isoleucyl-adenylate

6LDK の概要

• エントリーDOI: 10.2210/pdb6ldk/pdb
• 分子名称: Isoleucine--tRNA ligase, ADENOSINE MONOPHOSPHATE, ISOLEUCINE, ... (4 entities in total)
• 機能のキーワード: trna synthetase, translation
• 由来する生物種: Candida albicans SC5314
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 99829.76

構造登録者

Cho, Y.,Chung, S. (登録日: 2019-11-21, 公開日: 2020-11-04, 最終更新日: 2023-11-22)

主引用文献

Chung, S.,Kim, S.,Ryu, S.H.,Hwang, K.Y.,Cho, Y.
Structural Basis for the Antibiotic Resistance of Eukaryotic Isoleucyl-tRNA Synthetase.
Mol.Cells, 43:350-359, 2020

PubMed Abstract: Pathogenic aminoacyl-tRNA synthetases (ARSs) are attractive targets for anti-infective agents because their catalytic active sites are different from those of human ARSs. Mupirocin is a topical antibiotic that specifically inhibits bacterial isoleucy-ltRNA synthetase (IleRS), resulting in a block to protein synthesis. Previous studies on IleRS indicated that mupirocin-resistance of eukaryotic IleRS is primarily due to differences in two amino acids, His581 and Leu583, in the active site. However, without a eukaryotic IleRS structure, the structural basis for mupirocin-resistance of eukaryotic IleRS remains elusive. Herein, we determined the crystal structure of IleRS complexed with Ile-AMP at 2.9 Å resolution. The largest difference between eukaryotic and prokaryotic IleRS enzymes is closure of the active site pocket by Phe55 in the HIGH loop; Arg410 in the CP core loop; and the second Lys in the KMSKR loop. The Ile-AMP product is lodged in a closed active site, which may restrict its release and thereby enhance catalytic efficiency. The compact active site also prevents the optimal positioning of the 9-hydroxynonanoic acid of mupirocin and plays a critical role in resistance of eukaryotic IleRS to anti-infective agents.

PubMed: 32088946
DOI: 10.14348/molcells.2020.2287

実験手法

X-RAY DIFFRACTION (2.9 Å)