View source for 3cek


==Crystal structure of human dual specificity protein kinase (TTK)==
<StructureSection load='3cek' size='340' side='right'caption='[[3cek]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[3cek]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3CEK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3CEK FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=7PE:2-(2-(2-(2-(2-(2-ETHOXYETHOXY)ETHOXY)ETHOXY)ETHOXY)ETHOXY)ETHANOL'>7PE</scene></td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">TTK, MPS1L1 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Dual-specificity_kinase Dual-specificity kinase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.12.1 2.7.12.1] </span></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3cek FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3cek OCA], [https://pdbe.org/3cek PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3cek RCSB], [https://www.ebi.ac.uk/pdbsum/3cek PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3cek ProSAT]</span></td></tr>
</table>
== Function ==
[[https://www.uniprot.org/uniprot/TTK_HUMAN TTK_HUMAN]] Phosphorylates proteins on serine, threonine, and tyrosine. Probably associated with cell proliferation. Essential for chromosome alignment by enhancing AURKB activity (via direct CDCA8 phosphorylation) at the centromere, and for the mitotic checkpoint.<ref>PMID:18243099</ref>  
== 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/ce/3cek_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=3cek ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Mps1, a dual-specificity kinase, is required for the proper functioning of the spindle assembly checkpoint and for the maintenance of chromosomal stability. As Mps1 function has been implicated in numerous phases of the cell cycle, the development of a potent, selective small-molecule inhibitor of Mps1 should facilitate dissection of Mps1-related biology. We describe the cellular effects and Mps1 cocrystal structures of new, selective small-molecule inhibitors of Mps1. Consistent with RNAi studies, chemical inhibition of Mps1 leads to defects in Mad1 and Mad2 establishment at unattached kinetochores, decreased Aurora B kinase activity, premature mitotic exit and gross aneuploidy, without any evidence of centrosome duplication defects. However, in U2OS cells having extra centrosomes (an abnormality found in some cancers), Mps1 inhibition increases the frequency of multipolar mitoses. Lastly, Mps1 inhibitor treatment resulted in a decrease in cancer cell viability.

Small-molecule kinase inhibitors provide insight into Mps1 cell cycle function.,Kwiatkowski N, Jelluma N, Filippakopoulos P, Soundararajan M, Manak MS, Kwon M, Choi HG, Sim T, Deveraux QL, Rottmann S, Pellman D, Shah JV, Kops GJ, Knapp S, Gray NS Nat Chem Biol. 2010 May;6(5):359-68. Epub 2010 Apr 11. PMID:20383151<ref>PMID:20383151</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 3cek" style="background-color:#fffaf0;"></div>

==See Also==
*[[Dual specificity protein kinase 3D structures|Dual specificity protein kinase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Dual-specificity kinase]]
[[Category: Human]]
[[Category: Large Structures]]
[[Category: Arrowsmith, C H]]
[[Category: Bountra, C]]
[[Category: Delft, F von]]
[[Category: Edwards, A M]]
[[Category: Elkins, J M]]
[[Category: Fedorov, O]]
[[Category: Filippakopoulos, P]]
[[Category: Keates, T]]
[[Category: King, O]]
[[Category: Knapp, S]]
[[Category: Picaud, S S]]
[[Category: Pike, A C.W]]
[[Category: Pilka, E]]
[[Category: Roos, A]]
[[Category: Structural genomic]]
[[Category: Soundararajan, M]]
[[Category: Weigelt, J]]
[[Category: Atp-binding]]
[[Category: Dual specificity]]
[[Category: Esk]]
[[Category: Hmps1]]
[[Category: Kinase]]
[[Category: Nucleotide-binding]]
[[Category: Phosphoprotein]]
[[Category: Phosphotyrosine picked threonine kinase]]
[[Category: Pyt]]
[[Category: Serine/threonine-protein kinase]]
[[Category: Sgc]]
[[Category: Transferase]]
[[Category: Ttk]]
[[Category: Tyrosine-protein kinase]]