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< | ==Crystal Structure of eIF2alpha Protein Kinase GCN2: Wild-Type in Apo Form.== | ||
<StructureSection load='1zyc' size='340' side='right'caption='[[1zyc]], [[Resolution|resolution]] 3.00Å' scene=''> | |||
You may | == Structural highlights == | ||
<table><tr><td colspan='2'>[[1zyc]] is a 4 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=1ZYC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1ZYC 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]] 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=1zyc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1zyc OCA], [https://pdbe.org/1zyc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1zyc RCSB], [https://www.ebi.ac.uk/pdbsum/1zyc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1zyc ProSAT]</span></td></tr> | ||
</table> | |||
== Function == | |||
[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'. | |||
== Evolutionary Conservation == | |||
[[Image:Consurf_key_small.gif|200px|right]] | |||
Check<jmol> | |||
<jmolCheckbox> | |||
<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/zy/1zyc_consurf.spt"</scriptWhenChecked> | |||
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | |||
<text>to colour the structure by Evolutionary Conservation</text> | |||
</jmolCheckbox> | |||
</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=1zyc ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
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. | |||
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:15964839<ref>PMID:15964839</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 1zyc" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Serine/threonine protein kinase 3D structures|Serine/threonine protein kinase 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
== | [[Category: Large Structures]] | ||
== | |||
< | |||
[[Category: | |||
[[Category: Saccharomyces cerevisiae]] | [[Category: Saccharomyces cerevisiae]] | ||
[[Category: Burley | [[Category: Burley SK]] | ||
[[Category: Hinnebusch | [[Category: Hinnebusch AG]] | ||
[[Category: Padyana | [[Category: Padyana AK]] | ||
[[Category: Qiu | [[Category: Qiu H]] | ||
[[Category: Roll-Mecak | [[Category: Roll-Mecak A]] | ||
Latest revision as of 10:16, 23 August 2023
Crystal Structure of eIF2alpha Protein Kinase GCN2: Wild-Type in Apo Form.Crystal Structure of eIF2alpha Protein Kinase GCN2: Wild-Type in Apo Form.
Structural highlights
FunctionGCN2_YEAST Stimulates GCN4 translation in amino acid-starved cells by phosphorylating the alpha subunit of eIF-2 (SUI2) on 'Ser-52'. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedThe 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. 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:15964839[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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