4ye8: Difference between revisions

Latest revision as of 07:57, 27 September 2023

The crystal structure of the Y57H mutant of human GlnRS

Structural highlights

4ye8 is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 3.3Å
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.^[1]

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^[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Zhang X, Ling J, Barcia G, Jing L, Wu J, Barry BJ, Mochida GH, Hill RS, Weimer JM, Stein Q, Poduri A, Partlow JN, Ville D, Dulac O, Yu TW, Lam AT, Servattalab S, Rodriguez J, Boddaert N, Munnich A, Colleaux L, Zon LI, Soll D, Walsh CA, Nabbout R. Mutations in QARS, encoding glutaminyl-tRNA synthetase, cause progressive microcephaly, cerebral-cerebellar atrophy, and intractable seizures. Am J Hum Genet. 2014 Apr 3;94(4):547-58. doi: 10.1016/j.ajhg.2014.03.003. Epub, 2014 Mar 20. PMID:24656866 doi:https://dx.doi.org/10.1016/j.ajhg.2014.03.003
↑ 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. 2016 Feb 10. pii: gkw082. PMID:26869582 doi:https://dx.doi.org/10.1093/nar/gkw082

Proteopedia Page Contributors and Editors (what is this?)

OCA

[1] Zhang X, Ling J, Barcia G, Jing L, Wu J, Barry BJ, Mochida GH, Hill RS, Weimer JM, Stein Q, Poduri A, Partlow JN, Ville D, Dulac O, Yu TW, Lam AT, Servattalab S, Rodriguez J, Boddaert N, Munnich A, Colleaux L, Zon LI, Soll D, Walsh CA, Nabbout R. Mutations in QARS, encoding glutaminyl-tRNA synthetase, cause progressive microcephaly, cerebral-cerebellar atrophy, and intractable seizures. Am J Hum Genet. 2014 Apr 3;94(4):547-58. doi: 10.1016/j.ajhg.2014.03.003. Epub, 2014 Mar 20. PMID:24656866 doi:https://dx.doi.org/10.1016/j.ajhg.2014.03.003

[2] 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. 2016 Feb 10. pii: gkw082. PMID:26869582 doi:https://dx.doi.org/10.1093/nar/gkw082

[1]

[2]

@@ Line 4: / Line 4: @@
 == 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='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>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.3&#8491;</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 ==

4ye8: Difference between revisions

Latest revision as of 07:57, 27 September 2023

The crystal structure of the Y57H mutant of human GlnRS

Structural highlights

Disease

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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