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1om1

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[[Image:1om1.gif|left|200px]]<br /><applet load="1om1" size="350" color="white" frame="true" align="right" spinBox="true"
 
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caption="1om1, resolution 1.68&Aring;" />
 
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'''Crystal structure of maize CK2 alpha in complex with IQA'''<br />
 
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==Overview==
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==Crystal structure of maize CK2 alpha in complex with IQA==
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IQA [[5-oxo-5,6-dihydro-indolo(1,2-a)quinazolin-7-yl]acetic acid] is a novel ATP/GTP site-directed inhibitor of CK2 ('casein kinase 2'), a pleiotropic and constitutively active protein kinase whose activity is abnormally high in transformed cells. The K (i) value of IQA (0.17 microM) is lower than those of other CK2 inhibitors reported so far. Tested at 10 microM concentration in the presence of 100 microM ATP, IQA almost suppresses CK2 activity in vitro, whereas it is ineffective or weakly effective on a panel of 44 protein kinases and on phosphoinositide 3-kinase. In comparison, other CK2 inhibitors, notably apigenin and quercetin, are more promiscuous. The in vivo efficacy of IQA has been assessed by using the fact that treatment of Jurkat cells with IQA inhibits endogenous CK2 in a dose-dependent manner. IQA has been co-crystallized with maize CK2alpha, which is &gt;70% identical with its human homologue, and the structure of the complex has been determined at 1.68 A (1 A=0.1 nm) resolution. The inhibitor lies in the same plane occupied by the purine moiety of ATP with its more hydrophobic side facing the hinge region. Major contributions to the interaction are provided by hydrophobic forces and non-polar interactions involving the aromatic portion of the inhibitor and the hydrophobic residues surrounding the ATP-binding pocket, with special reference to the side chains of V53 (Val53), I66, M163 and I174. Consequently, mutants of human CK2alpha in which either V66 (the homologue of maize CK2alpha I66) or I174 is replaced by alanine are considerably less sensitive to IQA inhibition when compared with wild-type. These results provide new tools for deciphering the enigmatic role of CK2 in living cells and may pave the way for the development of drugs depending on CK2 activity.
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<StructureSection load='1om1' size='340' side='right'caption='[[1om1]], [[Resolution|resolution]] 1.68&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[1om1]] 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=1OM1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1OM1 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]] 1.68&#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=IQA:(5-OXO-5,6-DIHYDRO-INDOLO[1,2-A]QUINAZOLIN-7-YL)-ACETIC+ACID'>IQA</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=1om1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1om1 OCA], [https://pdbe.org/1om1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1om1 RCSB], [https://www.ebi.ac.uk/pdbsum/1om1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1om1 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/om/1om1_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=1om1 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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1OM1 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 <scene name='pdbligand=IQA:'>IQA</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. 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://oca.weizmann.ac.il/oca-bin/ocashort?id=1OM1 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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Biochemical and three-dimensional-structural study of the specific inhibition of protein kinase CK2 by [5-oxo-5,6-dihydroindolo-(1,2-a)quinazolin-7-yl]acetic acid (IQA)., Sarno S, de Moliner E, Ruzzene M, Pagano MA, Battistutta R, Bain J, Fabbro D, Schoepfer J, Elliott M, Furet P, Meggio F, Zanotti G, Pinna LA, Biochem J. 2003 Sep 15;374(Pt 3):639-46. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=12816539 12816539]
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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: Battistutta, R.]]
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[[Category: Battistutta R]]
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[[Category: Moliner, E De.]]
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[[Category: De Moliner E]]
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[[Category: Zanotti, G.]]
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[[Category: Zanotti G]]
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[[Category: IQA]]
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[[Category: ck2]]
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[[Category: inhibitor]]
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[[Category: iqa]]
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[[Category: zea mays]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:19:10 2008''
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Current revision

Crystal structure of maize CK2 alpha in complex with IQA

PDB ID 1om1

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