1JZS

Isoleucyl-tRNA synthetase Complexed with mupirocin

1JZS の概要

• エントリーDOI: 10.2210/pdb1jzs/pdb
• 関連するPDBエントリー: 1JZQ
• 分子名称: Isoleucyl-tRNA synthetase, ZINC ION, MUPIROCIN (3 entities in total)
• 機能のキーワード: aminoacyl-trna synthetase, riken structural genomics/proteomics initiative, rsgi, structural genomics, ligase
• 由来する生物種: Thermus thermophilus
• 細胞内の位置: Cytoplasm: P56690
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 95313.46

構造登録者

Nakama, T.,Nureki, O.,Yokoyama, S.,RIKEN Structural Genomics/Proteomics Initiative (RSGI) (登録日: 2001-09-17, 公開日: 2001-12-21, 最終更新日: 2024-10-23)

主引用文献

Nakama, T.,Nureki, O.,Yokoyama, S.
Structural basis for the recognition of isoleucyl-adenylate and an antibiotic, mupirocin, by isoleucyl-tRNA synthetase.
J.Biol.Chem., 276:47387-47393, 2001

PubMed Abstract: An analogue of isoleucyl-adenylate (Ile-AMS) potently inhibits the isoleucyl-tRNA synthetases (IleRSs) from the three primary kingdoms, whereas the antibiotic mupirocin inhibits only the eubacterial and archaeal IleRSs, but not the eukaryotic enzymes, and therefore is clinically used against methicillin-resistant Staphylococcus aureus. We determined the crystal structures of the IleRS from the thermophilic eubacterium, Thermus thermophilus, in complexes with Ile-AMS and mupirocin at 3.0- and 2.5-A resolutions, respectively. A structural comparison of the IleRS.Ile-AMS complex with the adenylate complexes of other aminoacyl-tRNA synthetases revealed the common recognition mode of aminoacyl-adenylate by the class I aminoacyl-tRNA synthetases. The Ile-AMS and mupirocin, which have significantly different chemical structures, are recognized by many of the same amino acid residues of the IleRS, suggesting that the antibiotic inhibits the enzymatic activity by blocking the binding site of the high energy intermediate, Ile-AMP. In contrast, the two amino acid residues that concomitantly recognize Ile-AMS and mupirocin are different between the eubacterial/archaeal IleRSs and the eukaryotic IleRSs. Mutagenic analyses revealed that the replacement of the two residues significantly changed the sensitivity to mupirocin.

PubMed: 11584022
DOI: 10.1074/jbc.M109089200

実験手法

X-RAY DIFFRACTION (2.5 Å)