6R1M

Crystal structure of E. coli seryl-tRNA synthetase complexed to seryl sulfamoyl adenosine

6R1M の概要

• エントリーDOI: 10.2210/pdb6r1m/pdb
• 分子名称: Serine--tRNA ligase, 5'-O-(N-(L-SERYL)-SULFAMOYL)ADENOSINE, PHOSPHATE ION, ... (5 entities in total)
• 機能のキーワード: aminoacyl-trna synthetase, class ii, protein synthesis, inhibitor, ligase
• 由来する生物種: Escherichia coli
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 100817.62

構造登録者

Salimraj, R.,Cain, R.,Roper, D.I. (登録日: 2019-03-14, 公開日: 2020-01-22, 最終更新日: 2024-01-24)

主引用文献

Cain, R.,Salimraj, R.,Punekar, A.S.,Bellini, D.,Fishwick, C.W.G.,Czaplewski, L.,Scott, D.J.,Harris, G.,Dowson, C.G.,Lloyd, A.J.,Roper, D.I.
Structure-Guided Enhancement of Selectivity of Chemical Probe Inhibitors Targeting Bacterial Seryl-tRNA Synthetase.
J.Med.Chem., 62:9703-9717, 2019

PubMed Abstract: Aminoacyl-tRNA synthetases are ubiquitous and essential enzymes for protein synthesis and also a variety of other metabolic processes, especially in bacterial species. Bacterial aminoacyl-tRNA synthetases represent attractive and validated targets for antimicrobial drug discovery if issues of prokaryotic versus eukaryotic selectivity and antibiotic resistance generation can be addressed. We have determined high-resolution X-ray crystal structures of the and seryl-tRNA synthetases in complex with aminoacyl adenylate analogues and applied a structure-based drug discovery approach to explore and identify a series of small molecule inhibitors that selectively inhibit bacterial seryl-tRNA synthetases with greater than 2 orders of magnitude compared to their human homologue, demonstrating a route to the selective chemical inhibition of these bacterial targets.

PubMed: 31626547
DOI: 10.1021/acs.jmedchem.9b01131

実験手法

X-RAY DIFFRACTION (1.5 Å)