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[[Image:3cek.jpg|left|200px]]


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==Crystal structure of human dual specificity protein kinase (TTK)==
The line below this paragraph, containing "STRUCTURE_3cek", creates the "Structure Box" on the page.
<StructureSection load='3cek' size='340' side='right'caption='[[3cek]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
You may change the PDB parameter (which sets the PDB file loaded into the applet)
== Structural highlights ==
or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
<table><tr><td colspan='2'>[[3cek]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. 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>
or leave the SCENE parameter empty for the default display.
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.3&#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=7PE:2-(2-(2-(2-(2-(2-ETHOXYETHOXY)ETHOXY)ETHOXY)ETHOXY)ETHOXY)ETHANOL'>7PE</scene></td></tr>
{{STRUCTURE_3cek|  PDB=3cek  |  SCENE=  }}
<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.


'''Crystal structure of human dual specificity protein kinase (TTK)'''
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>


==About this Structure==
==See Also==
3CEK is a [[Single protein]] structure of 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=3CEK OCA].
*[[Dual specificity protein kinase 3D structures|Dual specificity protein kinase 3D structures]]
[[Category: Dual-specificity kinase]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Single protein]]
[[Category: Large Structures]]
[[Category: Arrowsmith, C H.]]
[[Category: Arrowsmith CH]]
[[Category: Bountra, C.]]
[[Category: Bountra C]]
[[Category: Delft, F von.]]
[[Category: Edwards AM]]
[[Category: Edwards, A M.]]
[[Category: Elkins JM]]
[[Category: Elkins, J M.]]
[[Category: Fedorov O]]
[[Category: Fedorov, O.]]
[[Category: Filippakopoulos P]]
[[Category: Filippakopoulos, P.]]
[[Category: Keates T]]
[[Category: Keates, T.]]
[[Category: King O]]
[[Category: King, O.]]
[[Category: Knapp S]]
[[Category: Knapp, S.]]
[[Category: Picaud SS]]
[[Category: Picaud, S S.]]
[[Category: Pike ACW]]
[[Category: Pike, A C.W.]]
[[Category: Pilka E]]
[[Category: Pilka, E.]]
[[Category: Roos A]]
[[Category: Roos, A.]]
[[Category: Soundararajan M]]
[[Category: SGC, Structural Genomics Consortium.]]
[[Category: Weigelt J]]
[[Category: Soundararajan, M.]]
[[Category: Von Delft F]]
[[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: Polymorphism]]
[[Category: Pyt]]
[[Category: Serine/threonine-protein kinase]]
[[Category: Sgc]]
[[Category: Structural genomics consortium]]
[[Category: Transferase]]
[[Category: Ttk]]
[[Category: Tyrosine-protein kinase]]
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May  4 21:40:03 2008''

Latest revision as of 15:27, 30 August 2023

Crystal structure of human dual specificity protein kinase (TTK)Crystal structure of human dual specificity protein kinase (TTK)

Structural highlights

3cek is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.3Å
Ligands:
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

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.[1]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

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[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

See Also

References

  1. ↑ Jelluma N, Brenkman AB, van den Broek NJ, Cruijsen CW, van Osch MH, Lens SM, Medema RH, Kops GJ. Mps1 phosphorylates Borealin to control Aurora B activity and chromosome alignment. Cell. 2008 Jan 25;132(2):233-46. doi: 10.1016/j.cell.2007.11.046. PMID:18243099 doi:10.1016/j.cell.2007.11.046
  2. ↑ 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. Small-molecule kinase inhibitors provide insight into Mps1 cell cycle function. Nat Chem Biol. 2010 May;6(5):359-68. Epub 2010 Apr 11. PMID:20383151 doi:10.1038/nchembio.345

3cek, resolution 2.30Å

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