7K9M

Crystal structure of the complex of M. tuberculosis PheRS with cognate precursor tRNA and 5'-O-(N-phenylalanyl)sulfamoyl-adenosine

7K9M の概要

• エントリーDOI: 10.2210/pdb7k9m/pdb
• 関連するPDBエントリー: 7K98 7KA0
• 分子名称: Phenylalanine--tRNA ligase alpha subunit, Phenylalanine--tRNA ligase beta subunit, tRNA(Phe), ... (9 entities in total)
• 機能のキーワード: aminoacylation, phenylalanyl trna synthetase, adenylate analog, ligase-rna complex, structural genomics, center for structural genomics of infectious diseases, csgid, ligase/rna
• 由来する生物種: Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv); 詳細
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 152768.88

構造登録者

Michalska, K.,Chang, C.,Jedrzejczak, R.,Wower, J.,Baragana, B.,Forte, B.,Gilbert, I.H.,Joachimiak, A.,Center for Structural Genomics of Infectious Diseases (CSGID) (登録日: 2020-09-29, 公開日: 2021-05-12, 最終更新日: 2023-10-18)

主引用文献

Michalska, K.,Jedrzejczak, R.,Wower, J.,Chang, C.,Baragana, B.,Gilbert, I.H.,Forte, B.,Joachimiak, A.
Mycobacterium tuberculosis Phe-tRNA synthetase: structural insights into tRNA recognition and aminoacylation.
Nucleic Acids Res., 49:5351-5368, 2021

PubMed Abstract: Tuberculosis, caused by Mycobacterium tuberculosis, responsible for ∼1.5 million fatalities in 2018, is the deadliest infectious disease. Global spread of multidrug resistant strains is a public health threat, requiring new treatments. Aminoacyl-tRNA synthetases are plausible candidates as potential drug targets, because they play an essential role in translating the DNA code into protein sequence by attaching a specific amino acid to their cognate tRNAs. We report structures of M. tuberculosis Phe-tRNA synthetase complexed with an unmodified tRNAPhe transcript and either L-Phe or a nonhydrolyzable phenylalanine adenylate analog. High-resolution models reveal details of two modes of tRNA interaction with the enzyme: an initial recognition via indirect readout of anticodon stem-loop and aminoacylation ready state involving interactions of the 3' end of tRNAPhe with the adenylate site. For the first time, we observe the protein gate controlling access to the active site and detailed geometry of the acyl donor and tRNA acceptor consistent with accepted mechanism. We biochemically validated the inhibitory potency of the adenylate analog and provide the most complete view of the Phe-tRNA synthetase/tRNAPhe system to date. The presented topography of amino adenylate-binding and editing sites at different stages of tRNA binding to the enzyme provide insights for the rational design of anti-tuberculosis drugs.

PubMed: 33885823
DOI: 10.1093/nar/gkab272

実験手法

X-RAY DIFFRACTION (2.5 Å)