8C9E

Priestia megaterium mupirocin-sensitive isoleucyl-tRNA synthetase 1 complexed with an isoleucyl-adenylate analogue

8C9E の概要

• エントリーDOI: 10.2210/pdb8c9e/pdb
• 分子名称: Isoleucine--tRNA ligase, ZINC ION, N-[ISOLEUCINYL]-N'-[ADENOSYL]-DIAMINOSUFONE, ... (7 entities in total)
• 機能のキーワード: antibiotic, mupirocin-sensitive, ilers1, rna binding protein
• 由来する生物種: Priestia megaterium
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 106963.28

構造登録者

Brkic, A.,Leibundgut, M.,Jablonska, J.,Zanki, V.,Car, Z.,Petrovic Perokovic, V.,Ban, N.,Gruic-Sovulj, I. (登録日: 2023-01-21, 公開日: 2023-08-16, 最終更新日: 2024-03-27)

主引用文献

Brkic, A.,Leibundgut, M.,Jablonska, J.,Zanki, V.,Car, Z.,Petrovic Perokovic, V.,Marsavelski, A.,Ban, N.,Gruic-Sovulj, I.
Antibiotic hyper-resistance in a class I aminoacyl-tRNA synthetase with altered active site signature motif.
Nat Commun, 14:5498-5498, 2023

PubMed Abstract: Antibiotics target key biological processes that include protein synthesis. Bacteria respond by developing resistance, which increases rapidly due to antibiotics overuse. Mupirocin, a clinically used natural antibiotic, inhibits isoleucyl-tRNA synthetase (IleRS), an enzyme that links isoleucine to its tRNA for protein synthesis. Two IleRSs, mupirocin-sensitive IleRS1 and resistant IleRS2, coexist in bacteria. The latter may also be found in resistant Staphylococcus aureus clinical isolates. Here, we describe the structural basis of mupirocin resistance and unravel a mechanism of hyper-resistance evolved by some IleRS2 proteins. We surprisingly find that an up to 10-fold increase in resistance originates from alteration of the HIGH motif, a signature motif of the class I aminoacyl-tRNA synthetases to which IleRSs belong. The structural analysis demonstrates how an altered HIGH motif could be adopted in IleRS2 but not IleRS1, providing insight into an elegant mechanism for coevolution of the key catalytic motif and associated antibiotic resistance.

PubMed: 37679387
DOI: 10.1038/s41467-023-41244-3

実験手法

X-RAY DIFFRACTION (2.9 Å)