1lp4

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(New page: 200px<br /><applet load="1lp4" size="450" color="white" frame="true" align="right" spinBox="true" caption="1lp4, resolution 1.86&Aring;" /> '''Crystal structure of...)
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[[Image:1lp4.jpg|left|200px]]<br /><applet load="1lp4" size="450" color="white" frame="true" align="right" spinBox="true"
 
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caption="1lp4, resolution 1.86&Aring;" />
 
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'''Crystal structure of a binary complex of the catalytic subunit of protein kinase CK2 with Mg-AMPPNP'''<br />
 
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==Overview==
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==Crystal structure of a binary complex of the catalytic subunit of protein kinase CK2 with Mg-AMPPNP==
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Protein kinase CK2 (casein kinase 2) is a highly conserved and, ubiquitously found eukaryotic serine/threonine kinase that plays a role in, various cellular key processes like proliferation, apoptosis and circadian, rhythm. One of its prominent biochemical properties is its ability to use, GTP as well as ATP as a cosubstrate (dual-cosubstrate specificity). This, feature is exceptional among eukaryotic protein kinases, and its, biological significance is unknown. We describe here a mutant of the, catalytic subunit of protein kinase CK2 (CK2alpha) from Homo sapiens, (hsCK2alpha) with a clear and CK2-atypical preference for ATP compared to, GTP. This mutant was designed on the basis of several structures of, CK2alpha from Zea mays (zmCK2alpha) in complex with various, ATP-competitive ligands. A structural overlay revealed the existence of a, "purine base binding plane" harbouring the planar moiety of the respective, ligand like the purine base of ATP and GTP. This purine base binding plane, is sandwiched between the side-chains of Ile66 (Val66 in hsCK2alpha) and, Met163, and it adopts a significantly different orientation than in, prominent homologues like cAMP-dependent protein kinase (CAPK). By, exchanging these two flanking amino acids (Val66Ala, Met163Leu) in, hsCK2alpha(1-335), a C-terminally truncated variant of hsCK2alpha, the, cosubstrate specificity shifted in the expected direction so that the, mutant strongly favours ATP. A structure determination of the mutant in, complex with an ATP-analogue confirmed the predicted change of the purine, base binding plane orientation. An unexpected but in retrospect plausible, consequence of the mutagenesis was, that the helix alpha D region, which, is in the direct neighbourhood of the ATP-binding site, has adopted a, conformation that is more similar to CAPK and less favourable for binding, of GTP. These findings demonstrate that CK2alpha possesses sophisticated, structural adaptations in favour of dual-cosubstrate specificity, suggesting that this property could be of biological significance.
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<StructureSection load='1lp4' size='340' side='right'caption='[[1lp4]], [[Resolution|resolution]] 1.86&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[1lp4]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Zea_mays Zea mays]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1LP4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1LP4 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]] 1.86&#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=1lp4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1lp4 OCA], [https://pdbe.org/1lp4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1lp4 RCSB], [https://www.ebi.ac.uk/pdbsum/1lp4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1lp4 ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/CSK2A_MAIZE CSK2A_MAIZE] Casein kinases are operationally defined by their preferential utilization of acidic proteins such as caseins as substrates. The alpha chain contains the catalytic site.
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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/lp/1lp4_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=1lp4 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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1LP4 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Zea_mays Zea mays] 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=1LP4 OCA].
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*[[Casein kinase 3D structures|Casein kinase 3D structures]]
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__TOC__
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==Reference==
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</StructureSection>
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Inclining the purine base binding plane in protein kinase CK2 by exchanging the flanking side-chains generates a preference for ATP as a cosubstrate., Yde CW, Ermakova I, Issinger OG, Niefind K, J Mol Biol. 2005 Mar 25;347(2):399-414. Epub 2005 Jan 18. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=15740749 15740749]
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[[Category: Large Structures]]
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[[Category: Non-specific serine/threonine protein kinase]]
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[[Category: Single protein]]
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[[Category: Zea mays]]
[[Category: Zea mays]]
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[[Category: Guerra, B.]]
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[[Category: Guerra B]]
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[[Category: Issinger, O.G.]]
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[[Category: Issinger O-G]]
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[[Category: Niefind, K.]]
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[[Category: Niefind K]]
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[[Category: Puetter, M.]]
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[[Category: Puetter M]]
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[[Category: Schomburg, D.]]
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[[Category: Schomburg D]]
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[[Category: ANP]]
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[[Category: MG]]
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[[Category: casein kinase 2]]
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[[Category: ck2]]
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[[Category: dual-cosubstrate specificity]]
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[[Category: protein kinase]]
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''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Tue Nov 20 20:44:43 2007''
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Current revision

Crystal structure of a binary complex of the catalytic subunit of protein kinase CK2 with Mg-AMPPNP

PDB ID 1lp4

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