4YE9

The crystal structure of the G45V mutant of human GlnRS

Summary for 4YE9

• Entry DOI: 10.2210/pdb4ye9/pdb
• Related: 4YE6 4YE8
• Descriptor: Glutamine--tRNA ligase (2 entities in total)
• Functional Keywords: aminoacyl-trna synthetase, class i aars, glutamine, ligase
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 1
• Total formula weight: 88100.94

Authors

Ognjenovic, J.,Wu, J.,Ling, J.,Simonovic, M. (deposition date: 2015-02-23, release date: 2016-02-17, Last modification date: 2023-09-27)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.7 Å)