6nx4

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==Structure of the C-terminal Helical Repeat Domain of Eukaryotic Elongation Factor 2 Kinase (eEF-2K)==
==Structure of the C-terminal Helical Repeat Domain of Eukaryotic Elongation Factor 2 Kinase (eEF-2K)==
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<StructureSection load='6nx4' size='340' side='right'caption='[[6nx4]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''>
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<StructureSection load='6nx4' size='340' side='right'caption='[[6nx4]]' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>[[6nx4]] is a 1 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6NX4 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6NX4 FirstGlance]. <br>
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<table><tr><td colspan='2'>[[6nx4]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6NX4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6NX4 FirstGlance]. <br>
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</td></tr><tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/[Elongation_factor_2]_kinase [Elongation factor 2] kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.20 2.7.11.20] </span></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">Solution NMR</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=6nx4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6nx4 OCA], [http://pdbe.org/6nx4 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6nx4 RCSB], [http://www.ebi.ac.uk/pdbsum/6nx4 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6nx4 ProSAT]</span></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=6nx4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6nx4 OCA], [https://pdbe.org/6nx4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6nx4 RCSB], [https://www.ebi.ac.uk/pdbsum/6nx4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6nx4 ProSAT]</span></td></tr>
</table>
</table>
== Function ==
== Function ==
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[[http://www.uniprot.org/uniprot/EF2K_HUMAN EF2K_HUMAN]] Threonine kinase that regulates protein synthesis by controlling the rate of peptide chain elongation. Upon activation by a variety of upstream kinases including AMPK or TRPM7, phosphorylates the elongation factor EEF2 at a single site, renders it unable to bind ribosomes and thus inactive. In turn, the rate of protein synthesis is reduced.<ref>PMID:14709557</ref> <ref>PMID:9144159</ref>
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[https://www.uniprot.org/uniprot/EF2K_HUMAN EF2K_HUMAN] Threonine kinase that regulates protein synthesis by controlling the rate of peptide chain elongation. Upon activation by a variety of upstream kinases including AMPK or TRPM7, phosphorylates the elongation factor EEF2 at a single site, renders it unable to bind ribosomes and thus inactive. In turn, the rate of protein synthesis is reduced.<ref>PMID:14709557</ref> <ref>PMID:9144159</ref>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Eukaryotic elongation factor 2 kinase (eEF-2K), an atypical calmodulin-activated protein kinase, regulates translational elongation by phosphorylating its substrate, eukaryotic elongation factor 2 (eEF-2), thereby reducing its affinity for the ribosome. The activation and activity of eEF-2K are critical for survival under energy-deprived conditions and is implicated in a variety of essential physiological processes. Previous biochemical experiments have indicated that the binding site for the substrate eEF-2 is located in the C-terminal domain of eEF-2K, a region predicted to harbor several alpha-helical repeats. Here, using NMR methodology we have determined the solution structure of a C-terminal fragment of eEF-2K, eEF-2K562-725 that encodes two alpha-helical repeats. The structure of eEF-2K562-725 shows signatures characteristic of TPR domains and of their SEL1-like sub-family. Further, using the analyses of NMR spectral perturbations and ITC measurements, we have localized the eEF-2 binding site on eEF-2K562-725. We find that eEF-2K562-725 engages eEF-2 with an affinity comparable to that of the full-length enzyme. Further, eEF-2K562-725 is able to inhibit the phosphorylation of eEF-2 by full-length eEF-2K in trans. Our present studies establish that eEF-2K562-725 encodes the major elements necessary to enable the eEF-2K/eEF-2 interactions.
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Solution Structure of the Carboxy-Terminal Tandem Repeat Domain of Eukaryotic Elongation Factor 2 Kinase and its Role in Substrate Recognition.,Piserchio A, Will N, Giles DH, Hajredini F, Dalby KN, Ghose R J Mol Biol. 2019 May 17. pii: S0022-2836(19)30290-6. doi:, 10.1016/j.jmb.2019.05.019. PMID:31108082<ref>PMID:31108082</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 6nx4" style="background-color:#fffaf0;"></div>
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== References ==
== References ==
<references/>
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
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[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Large Structures]]
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[[Category: Dalby, K N]]
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[[Category: Dalby KN]]
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[[Category: Ghose, R]]
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[[Category: Ghose R]]
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[[Category: Giles, D H]]
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[[Category: Giles DH]]
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[[Category: Hajredini, F]]
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[[Category: Hajredini F]]
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[[Category: Piserchio, A]]
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[[Category: Piserchio A]]
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[[Category: Will, N]]
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[[Category: Will N]]
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[[Category: Binding domain]]
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[[Category: Eef2]]
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[[Category: Eef2k]]
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[[Category: Elongation]]
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[[Category: Kinase]]
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[[Category: Sel1]]
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[[Category: Tpr]]
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[[Category: Transferase]]
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[[Category: Translation]]
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Current revision

Structure of the C-terminal Helical Repeat Domain of Eukaryotic Elongation Factor 2 Kinase (eEF-2K)

PDB ID 6nx4

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