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| | <StructureSection load='2zmd' size='340' side='right'caption='[[2zmd]], [[Resolution|resolution]] 2.88Å' scene=''> | | <StructureSection load='2zmd' size='340' side='right'caption='[[2zmd]], [[Resolution|resolution]] 2.88Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2zmd]] 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=2ZMD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2ZMD FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2zmd]] 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=2ZMD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2ZMD FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=537:2,6-DIHYDROANTHRA/1,9-CD/PYRAZOL-6-ONE'>537</scene>, <scene name='pdbligand=7PE:2-(2-(2-(2-(2-(2-ETHOXYETHOXY)ETHOXY)ETHOXY)ETHOXY)ETHOXY)ETHANOL'>7PE</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.88Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[2zmc|2zmc]]</div></td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=537:2,6-DIHYDROANTHRA/1,9-CD/PYRAZOL-6-ONE'>537</scene>, <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=2zmd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2zmd OCA], [https://pdbe.org/2zmd PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2zmd RCSB], [https://www.ebi.ac.uk/pdbsum/2zmd PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2zmd ProSAT]</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=2zmd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2zmd OCA], [https://pdbe.org/2zmd PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2zmd RCSB], [https://www.ebi.ac.uk/pdbsum/2zmd PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2zmd ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == 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>
| + | [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 == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Dual-specificity kinase]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Human]]
| + | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Chavas, L M.G]] | + | [[Category: Chavas LMG]] |
| - | [[Category: Chu, M L.H]] | + | [[Category: Chu MLH]] |
| - | [[Category: Douglas, K T]] | + | [[Category: Douglas KT]] |
| - | [[Category: Eyers, P A]] | + | [[Category: Eyers PA]] |
| - | [[Category: Tabernero, L]] | + | [[Category: Tabernero L]] |
| - | [[Category: Atp-binding]]
| + | |
| - | [[Category: Kinase]]
| + | |
| - | [[Category: Mps1]]
| + | |
| - | [[Category: Nucleotide-binding]]
| + | |
| - | [[Category: Phosphoprotein]]
| + | |
| - | [[Category: Serine/threonine-protein kinase]]
| + | |
| - | [[Category: Sp600125]]
| + | |
| - | [[Category: T686a]]
| + | |
| - | [[Category: Transferase]]
| + | |
| - | [[Category: Tyrosine-protein kinase]]
| + | |
| Structural highlights
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
Chromosomal instability can result from defective control of checkpoints and is associated with malignant cell growth. Monopolar spindle 1 (Mps1) is a dual-specificity protein kinase that has important roles in the prevention of aneuploidy during the cell cycle and might therefore be a potential target for new therapeutic agents in the treatment of cancer. To gain insights into the molecular mechanism of Mps1 inhibition by small molecules, we determined the x-ray structure of Mps1, both alone and in complex with the ATP-competitive inhibitor SP600125. Mps1 adopts a classic protein kinase fold, with the inhibitor sitting in the ATP-binding site where it is stabilized by hydrophobic interactions. We identified a secondary pocket, not utilized by SP600125, which might be exploited for the rational design of specific Mps1 inhibitors. These structures provide important insights into the interaction of this protein kinase with small molecules and suggest potential mechanisms for Mps1 regulation.
Crystal structure of the catalytic domain of the mitotic checkpoint kinase Mps1 in complex with SP600125.,Chu ML, Chavas LM, Douglas KT, Eyers PA, Tabernero L J Biol Chem. 2008 Aug 1;283(31):21495-500. Epub 2008 May 14. PMID:18480048[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ 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
- ↑ Chu ML, Chavas LM, Douglas KT, Eyers PA, Tabernero L. Crystal structure of the catalytic domain of the mitotic checkpoint kinase Mps1 in complex with SP600125. J Biol Chem. 2008 Aug 1;283(31):21495-500. Epub 2008 May 14. PMID:18480048 doi:http://dx.doi.org/10.1074/jbc.M803026200
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