2wqe

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[[Image:2wqe.png|left|200px]]
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==STRUCTURE OF S155R AURORA-A SOMATIC MUTANT==
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<StructureSection load='2wqe' size='340' side='right' caption='[[2wqe]], [[Resolution|resolution]] 2.50&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[2wqe]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2WQE OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2WQE FirstGlance]. <br>
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</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ADP:ADENOSINE-5-DIPHOSPHATE'>ADP</scene><br>
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<tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2w1g|2w1g]], [[1muo|1muo]], [[2j50|2j50]], [[1ol7|1ol7]], [[2w1d|2w1d]], [[1ol6|1ol6]], [[2w1e|2w1e]], [[2bmc|2bmc]], [[2c6e|2c6e]], [[2j4z|2j4z]], [[1ol5|1ol5]], [[2w1f|2w1f]], [[2c6d|2c6d]], [[2w1c|2w1c]], [[1mq4|1mq4]]</td></tr>
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<tr><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><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>
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<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2wqe FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2wqe OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2wqe RCSB], [http://www.ebi.ac.uk/pdbsum/2wqe PDBsum]</span></td></tr>
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<table>
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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/wq/2wqe_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/chain_selection.php?pdb_ID=2ata ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Mutations in protein kinases can drive cancer through alterations of the kinase activity or by uncoupling kinase activity from regulation. Changes to protein expression in Aurora A, a mitotic Ser/Thr kinase, are associated with the development of several human cancers, but the effects of somatic cancer-associated mutations have not been determined. In this study we show that Aurora A kinase activity is altered in different ways in three somatic cancer-associated mutations located within the catalytic domain; Aurora A(V174M) shows constitutively increased kinase activity, Aurora A(S155R) activity is decreased primarily due to misregulation, and Aurora A(S361*) activity is ablated due to loss of structural integrity. These alterations suggest vastly different mechanisms for the role of these three mutations in human cancer. We have further characterized the Aurora A(S155R) mutant protein, found that its reduced cellular activity and mislocalization are due to loss of interaction with TPX2, and deciphered the structural basis of the disruption at 2.5 A resolution. Previous studies have shown that disruption of the Aurora A/TPX2 interaction results in defective spindles that generate chromosomal abnormalities. In a panel of 40 samples from microsatellite instability-positive colon cancer patients, we found one example in which the tumor contained only Aurora A(S155R), whereas the normal tissue contained only wild-type Aurora A. We propose that the S155R mutation is an example of a somatic mutation associated with this tumor type, albeit at modest frequency, that could promote aneuploidy through the loss of regulated interactions between Aurora A and its protein partners.
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{{STRUCTURE_2wqe| PDB=2wqe | SCENE= }}
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A cancer-associated aurora A mutant is mislocalized and misregulated due to loss of interaction with TPX2.,Bibby RA, Tang C, Faisal A, Drosopoulos K, Lubbe S, Houlston R, Bayliss R, Linardopoulos S J Biol Chem. 2009 Nov 27;284(48):33177-84. Epub 2009 Oct 2. PMID:19801554<ref>PMID:19801554</ref>
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===STRUCTURE OF S155R AURORA-A SOMATIC MUTANT===
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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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{{ABSTRACT_PUBMED_19801554}}
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==See Also==
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*[[Serine/threonine protein kinase|Serine/threonine protein kinase]]
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==About this Structure==
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== References ==
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[[2wqe]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2WQE OCA].
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<references/>
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__TOC__
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==Reference==
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</StructureSection>
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<ref group="xtra">PMID:019801554</ref><references group="xtra"/>
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[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Non-specific serine/threonine protein kinase]]
[[Category: Non-specific serine/threonine protein kinase]]

Revision as of 02:11, 1 October 2014

STRUCTURE OF S155R AURORA-A SOMATIC MUTANT

2wqe, resolution 2.50Å

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