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| - | [[Image:1lp4.jpg|left|200px]] | |
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| - | {{Structure
| + | ==Crystal structure of a binary complex of the catalytic subunit of protein kinase CK2 with Mg-AMPPNP== |
| - | |PDB= 1lp4 |SIZE=350|CAPTION= <scene name='initialview01'>1lp4</scene>, resolution 1.86Å
| + | <StructureSection load='1lp4' size='340' side='right'caption='[[1lp4]], [[Resolution|resolution]] 1.86Å' scene=''> |
| - | |SITE=
| + | == Structural highlights == |
| - | |LIGAND= <scene name='pdbligand=ANP:PHOSPHOAMINOPHOSPHONIC+ACID-ADENYLATE+ESTER'>ANP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>
| + | <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> |
| - | |ACTIVITY= <span class='plainlinks'>[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] </span>
| + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.86Å</td></tr> |
| - | |GENE=
| + | <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> |
| - | |DOMAIN=
| + | <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> |
| - | |RELATEDENTRY=[[1lpu|1LPU]], [[1lr4|1LR4]], [[1daw|1DAW]], [[1day|1DAY]], [[1jwh|1JWH]], [[1qf8|1QF8]]
| + | </table> |
| - | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1lp4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1lp4 OCA], [http://www.ebi.ac.uk/pdbsum/1lp4 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1lp4 RCSB]</span>
| + | == Function == |
| - | }}
| + | [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. |
| | + | == 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/lp/1lp4_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=1lp4 ConSurf]. |
| | + | <div style="clear:both"></div> |
| | | | |
| - | '''Crystal structure of a binary complex of the catalytic subunit of protein kinase CK2 with Mg-AMPPNP'''
| + | ==See Also== |
| - | | + | *[[Casein kinase 3D structures|Casein kinase 3D structures]] |
| - | | + | __TOC__ |
| - | ==Overview== | + | </StructureSection> |
| - | 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.
| + | [[Category: Large Structures]] |
| - | | + | |
| - | ==About this Structure==
| + | |
| - | 1LP4 is a [[Single protein]] structure of sequence from [http://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].
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| - | | + | |
| - | ==Reference==
| + | |
| - | 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://www.ncbi.nlm.nih.gov/pubmed/15740749 15740749]
| + | |
| - | [[Category: Non-specific serine/threonine protein kinase]]
| + | |
| - | [[Category: Single protein]] | + | |
| | [[Category: Zea mays]] | | [[Category: Zea mays]] |
| - | [[Category: Guerra, B.]] | + | [[Category: Guerra B]] |
| - | [[Category: Issinger, O G.]] | + | [[Category: Issinger O-G]] |
| - | [[Category: Niefind, K.]] | + | [[Category: Niefind K]] |
| - | [[Category: Puetter, M.]] | + | [[Category: Puetter M]] |
| - | [[Category: Schomburg, D.]] | + | [[Category: Schomburg D]] |
| - | [[Category: casein kinase 2]]
| + | |
| - | [[Category: ck2]]
| + | |
| - | [[Category: dual-cosubstrate specificity]]
| + | |
| - | [[Category: protein kinase]]
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| - | | + | |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 22:05:33 2008''
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