4YE9

The crystal structure of the G45V mutant of human GlnRS

4YE9 の概要

• エントリーDOI: 10.2210/pdb4ye9/pdb
• 関連するPDBエントリー: 4YE6 4YE8
• 分子名称: Glutamine--tRNA ligase (2 entities in total)
• 機能のキーワード: aminoacyl-trna synthetase, class i aars, glutamine, ligase
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 88100.94

構造登録者

Ognjenovic, J.,Wu, J.,Ling, J.,Simonovic, M. (登録日: 2015-02-23, 公開日: 2016-02-17, 最終更新日: 2023-09-27)

主引用文献

Ognjenovic, J.,Wu, J.,Matthies, D.,Baxa, U.,Subramaniam, S.,Ling, J.,Simonovic, M.
The crystal structure of human GlnRS provides basis for the development of neurological disorders.
Nucleic Acids Res., 44:3420-3431, 2016

PubMed Abstract: Cytosolic glutaminyl-tRNA synthetase (GlnRS) is the singular enzyme responsible for translation of glutamine codons. Compound heterozygous mutations in GlnRS cause severe brain disorders by a poorly understood mechanism. Herein, we present crystal structures of the wild type and two pathological mutants of human GlnRS, which reveal, for the first time, the domain organization of the intact enzyme and the structure of the functionally important N-terminal domain (NTD). Pathological mutations mapping in the NTD alter the domain structure, and decrease catalytic activity and stability of GlnRS, whereas missense mutations in the catalytic domain induce misfolding of the enzyme. Our results suggest that the reduced catalytic efficiency and a propensity of GlnRS mutants to misfold trigger the disease development. This report broadens the spectrum of brain pathologies elicited by protein misfolding and provides a paradigm for understanding the role of mutations in aminoacyl-tRNA synthetases in neurological diseases.

PubMed: 26869582
DOI: 10.1093/nar/gkw082

実験手法

X-RAY DIFFRACTION (2.7 Å)