4ye8: Difference between revisions
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The | ==The crystal structure of the Y57H mutant of human GlnRS== | ||
<StructureSection load='4ye8' size='340' side='right'caption='[[4ye8]], [[Resolution|resolution]] 3.30Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[4ye8]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4YE8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4YE8 FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.3Å</td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4ye8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ye8 OCA], [https://pdbe.org/4ye8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4ye8 RCSB], [https://www.ebi.ac.uk/pdbsum/4ye8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4ye8 ProSAT]</span></td></tr> | |||
</table> | |||
== Disease == | |||
[https://www.uniprot.org/uniprot/SYQ_HUMAN SYQ_HUMAN] The disease is caused by mutations affecting the gene represented in this entry. | |||
== Function == | |||
[https://www.uniprot.org/uniprot/SYQ_HUMAN SYQ_HUMAN] Plays a critical role in brain development.<ref>PMID:24656866</ref> | |||
<div style="background-color:#fffaf0;"> | |||
== 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<ref>PMID:26869582</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: Ognjenovic J | <div class="pdbe-citations 4ye8" style="background-color:#fffaf0;"></div> | ||
==See Also== | |||
*[[Aminoacyl tRNA synthetase 3D structures|Aminoacyl tRNA synthetase 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: Ling J]] | |||
[[Category: Ognjenovic J]] | |||
[[Category: Simonovic M]] | |||
[[Category: Wu J]] | |||
Latest revision as of 10:57, 27 September 2023
The crystal structure of the Y57H mutant of human GlnRSThe crystal structure of the Y57H mutant of human GlnRS
Structural highlights
DiseaseSYQ_HUMAN The disease is caused by mutations affecting the gene represented in this entry. FunctionSYQ_HUMAN Plays a critical role in brain development.[1] Publication Abstract from PubMedCytosolic 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[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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