4ye8

The crystal structure of the Y57H mutant of human GlnRS

spinqualitylabelsall models 4ye8, resolution 3.30Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4ye8 is a 1 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Related: 4ye6, 4ye9 Gene: QARS (HUMAN) Activity: Glutamine--tRNA ligase, with EC number 6.1.1.18 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Disease [SYQ_HUMAN] The disease is caused by mutations affecting the gene represented in this entry. Function [SYQ_HUMAN] Plays a critical role in brain development. Publication Abstract from PubMed 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. The crystal structure of human GlnRS provides basis for the development of neurological disorders.,Ognjenovic J, Wu J, Matthies D, Baxa U, Subramaniam S, Ling J, Simonovic M Nucleic Acids Res. 2016 Feb 10. pii: gkw082. PMID:26869582 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Aminoacyl tRNA synthetase 3D structures

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