2zt5

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==Crystal structure of human glycyl-trna synthetase (GLYRS) in complex with AP4A (cocrystallized with ATP)==
==Crystal structure of human glycyl-trna synthetase (GLYRS) in complex with AP4A (cocrystallized with ATP)==
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<StructureSection load='2zt5' size='340' side='right' caption='[[2zt5]], [[Resolution|resolution]] 2.50&Aring;' scene=''>
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<StructureSection load='2zt5' size='340' side='right'caption='[[2zt5]], [[Resolution|resolution]] 2.50&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>[[2zt5]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2ZT5 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2ZT5 FirstGlance]. <br>
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<table><tr><td colspan='2'>[[2zt5]] 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=2ZT5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2ZT5 FirstGlance]. <br>
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=B4P:BIS(ADENOSINE)-5-TETRAPHOSPHATE'>B4P</scene></td></tr>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.5&#8491;</td></tr>
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<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2pme|2pme]], [[2pmf|2pmf]], [[2zt6|2zt6]], [[2zt7|2zt7]], [[2zt8|2zt8]]</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=B4P:BIS(ADENOSINE)-5-TETRAPHOSPHATE'>B4P</scene></td></tr>
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<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">GARS ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2zt5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2zt5 OCA], [https://pdbe.org/2zt5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2zt5 RCSB], [https://www.ebi.ac.uk/pdbsum/2zt5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2zt5 ProSAT]</span></td></tr>
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<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Glycine--tRNA_ligase Glycine--tRNA ligase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=6.1.1.14 6.1.1.14] </span></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2zt5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2zt5 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2zt5 RCSB], [http://www.ebi.ac.uk/pdbsum/2zt5 PDBsum]</span></td></tr>
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</table>
</table>
== Disease ==
== Disease ==
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[[http://www.uniprot.org/uniprot/SYG_HUMAN SYG_HUMAN]] Defects in GARS are the cause of Charcot-Marie-Tooth disease type 2D (CMT2D) [MIM:[http://omim.org/entry/601472 601472]]. CMT2D is a form of Charcot-Marie-Tooth disease, the most common inherited disorder of the peripheral nervous system. Charcot-Marie-Tooth disease is classified in two main groups on the basis of electrophysiologic properties and histopathology: primary peripheral demyelinating neuropathy or CMT1, and primary peripheral axonal neuropathy or CMT2. Neuropathies of the CMT2 group are characterized by signs of axonal regeneration in the absence of obvious myelin alterations, normal or slightly reduced nerve conduction velocities, and progressive distal muscle weakness and atrophy. CMT2D is characterized by a more severe phenotype in the upper extremities (severe weakness and atrophy, absence of tendon reflexes) than in the lower limbs. CMT2D inheritance is autosomal dominant.<ref>PMID:12690580</ref> Defects in GARS are a cause of distal hereditary motor neuronopathy type 5A (HMN5A) [MIM:[http://omim.org/entry/600794 600794]]; also known as distal hereditary motor neuropathy type V (DSMAV). A disorder characterized by distal muscular atrophy mainly affecting the upper extremities, in contrast to other distal motor neuronopathies. These constitute a heterogeneous group of neuromuscular diseases caused by selective degeneration of motor neurons in the anterior horn of the spinal cord, without sensory deficit in the posterior horn. The overall clinical picture consists of a classical distal muscular atrophy syndrome in the legs without clinical sensory loss. The disease starts with weakness and wasting of distal muscles of the anterior tibial and peroneal compartments of the legs. Later on, weakness and atrophy may expand to the proximal muscles of the lower limbs and/or to the distal upper limbs.<ref>PMID:12690580</ref>
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[https://www.uniprot.org/uniprot/GARS_HUMAN GARS_HUMAN] Autosomal dominant Charcot-Marie-Tooth disease type 2D;Distal hereditary motor neuropathy type 5. The disease is caused by variants affecting the gene represented in this entry. The disease is caused by variants affecting the gene represented in this entry. The disease is caused by variants affecting the gene represented in this entry.
== Function ==
== Function ==
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[[http://www.uniprot.org/uniprot/SYG_HUMAN SYG_HUMAN]] Catalyzes the attachment of glycine to tRNA(Gly). Is also able produce diadenosine tetraphosphate (Ap4A), a universal pleiotropic signaling molecule needed for cell regulation pathways, by direct condensation of 2 ATPs.<ref>PMID:19710017</ref>
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[https://www.uniprot.org/uniprot/GARS_HUMAN GARS_HUMAN] Catalyzes the ATP-dependent ligation of glycine to the 3'-end of its cognate tRNA, via the formation of an aminoacyl-adenylate intermediate (Gly-AMP) (PubMed:17544401, PubMed:28675565, PubMed:24898252). Also produces diadenosine tetraphosphate (Ap4A), a universal pleiotropic signaling molecule needed for cell regulation pathways, by direct condensation of 2 ATPs. Thereby, may play a special role in Ap4A homeostasis (PubMed:19710017).<ref>PMID:17544401</ref> <ref>PMID:19710017</ref> <ref>PMID:24898252</ref> <ref>PMID:28675565</ref>
== Evolutionary Conservation ==
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
Check<jmol>
<jmolCheckbox>
<jmolCheckbox>
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<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/zt/2zt5_consurf.spt"</scriptWhenChecked>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/zt/2zt5_consurf.spt"</scriptWhenChecked>
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
<text>to colour the structure by Evolutionary Conservation</text>
<text>to colour the structure by Evolutionary Conservation</text>
</jmolCheckbox>
</jmolCheckbox>
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</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/chain_selection.php?pdb_ID=2ata ConSurf].
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</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2zt5 ConSurf].
<div style="clear:both"></div>
<div style="clear:both"></div>
==See Also==
==See Also==
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*[[Aminoacyl tRNA Synthetase|Aminoacyl tRNA Synthetase]]
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*[[Aminoacyl tRNA synthetase 3D structures|Aminoacyl tRNA synthetase 3D structures]]
== References ==
== References ==
<references/>
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
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[[Category: Glycine--tRNA ligase]]
 
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Guo, R T]]
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[[Category: Large Structures]]
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[[Category: Schimmel, P]]
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[[Category: Guo RT]]
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[[Category: Yang, X L]]
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[[Category: Schimmel P]]
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[[Category: Aminoacyl-trna synthetase]]
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[[Category: Yang XL]]
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[[Category: Ap4a]]
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[[Category: Atp-binding]]
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[[Category: Charcot-marie-tooth disease]]
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[[Category: Disease mutation]]
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[[Category: Gly-amp]]
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[[Category: Glycine]]
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[[Category: Ligase]]
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[[Category: Nucleotide-binding]]
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[[Category: Phosphoprotein]]
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[[Category: Protein biosynthesis]]
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[[Category: Trna]]
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Current revision

Crystal structure of human glycyl-trna synthetase (GLYRS) in complex with AP4A (cocrystallized with ATP)

PDB ID 2zt5

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OCA

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