1zy5

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(New page: 200px<br /><applet load="1zy5" size="450" color="white" frame="true" align="right" spinBox="true" caption="1zy5, resolution 2.00&Aring;" /> '''Crystal Structure of...)
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[[Image:1zy5.gif|left|200px]]<br /><applet load="1zy5" size="450" color="white" frame="true" align="right" spinBox="true"
 
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caption="1zy5, resolution 2.00&Aring;" />
 
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'''Crystal Structure of eIF2alpha Protein Kinase GCN2: R794G Hyperactivating Mutant Complexed with AMPPNP.'''<br />
 
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==Overview==
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==Crystal Structure of eIF2alpha Protein Kinase GCN2: R794G Hyperactivating Mutant Complexed with AMPPNP.==
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The GCN2 protein kinase coordinates protein synthesis with levels of amino, acid stores by phosphorylating eukaryotic translation initiation factor 2., The autoinhibited form of GCN2 is activated in cells starved of amino, acids by binding of uncharged tRNA to a histidyl-tRNA synthetase-like, domain. Replacement of Arg-794 with Gly in the PK domain (R794G) activates, GCN2 independently of tRNA binding. Crystal structures of the GCN2 protein, kinase domain have been determined for wild-type and R794G mutant forms in, the apo state and bound to ATP/AMPPNP. These structures reveal that GCN2, autoinhibition results from stabilization of a closed conformation that, restricts ATP binding. The R794G mutant shows increased flexibility in the, hinge region connecting the N- and C-lobes, resulting from loss of, multiple interactions involving Arg794. This conformational change is, associated with intradomain movement that enhances ATP binding and, hydrolysis. We propose that intramolecular interactions following tRNA, binding remodel the hinge region in a manner similar to the mechanism of, enzyme activation elicited by the R794G mutation.
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<StructureSection load='1zy5' size='340' side='right'caption='[[1zy5]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[1zy5]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Saccharomyces_cerevisiae Saccharomyces cerevisiae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1ZY5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1ZY5 FirstGlance]. <br>
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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&#8491;</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=ANP:PHOSPHOAMINOPHOSPHONIC+ACID-ADENYLATE+ESTER'>ANP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></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=1zy5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1zy5 OCA], [https://pdbe.org/1zy5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1zy5 RCSB], [https://www.ebi.ac.uk/pdbsum/1zy5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1zy5 ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/GCN2_YEAST GCN2_YEAST] Stimulates GCN4 translation in amino acid-starved cells by phosphorylating the alpha subunit of eIF-2 (SUI2) on 'Ser-52'.
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/zy/1zy5_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</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/main_output.php?pdb_ID=1zy5 ConSurf].
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<div style="clear:both"></div>
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==About this Structure==
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==See Also==
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1ZY5 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Saccharomyces_cerevisiae Saccharomyces cerevisiae] with MG and ANP as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1ZY5 OCA].
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*[[Serine/threonine protein kinase 3D structures|Serine/threonine protein kinase 3D structures]]
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__TOC__
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==Reference==
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</StructureSection>
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Structural basis for autoinhibition and mutational activation of eukaryotic initiation factor 2alpha protein kinase GCN2., Padyana AK, Qiu H, Roll-Mecak A, Hinnebusch AG, Burley SK, J Biol Chem. 2005 Aug 12;280(32):29289-99. Epub 2005 Jun 17. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=15964839 15964839]
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[[Category: Large Structures]]
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[[Category: Non-specific serine/threonine protein kinase]]
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[[Category: Saccharomyces cerevisiae]]
[[Category: Saccharomyces cerevisiae]]
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[[Category: Single protein]]
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[[Category: Burley SK]]
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[[Category: Burley, S.K.]]
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[[Category: Hinnebusch AG]]
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[[Category: Hinnebusch, A.G.]]
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[[Category: Padyana AK]]
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[[Category: Padyana, A.K.]]
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[[Category: Qiu H]]
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[[Category: Qiu, H.]]
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[[Category: Roll-Mecak A]]
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[[Category: Roll-Mecak, A.]]
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[[Category: ANP]]
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[[Category: MG]]
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[[Category: amino-acid starvation]]
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[[Category: eif2alpha kinase]]
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[[Category: protein kinase]]
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[[Category: signal transduction]]
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[[Category: starvation stress response]]
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[[Category: translation regulator]]
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''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Wed Nov 21 07:43:54 2007''
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Current revision

Crystal Structure of eIF2alpha Protein Kinase GCN2: R794G Hyperactivating Mutant Complexed with AMPPNP.

PDB ID 1zy5

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