3CEK
Crystal structure of human dual specificity protein kinase (TTK)
Summary for 3CEK
| Entry DOI | 10.2210/pdb3cek/pdb |
| Descriptor | Dual specificity protein kinase TTK, 2-(2-(2-(2-(2-(2-ETHOXYETHOXY)ETHOXY)ETHOXY)ETHOXY)ETHOXY)ETHANOL (3 entities in total) |
| Functional Keywords | ttk, hmps1, pyt, esk, kinase, dual specificity, phosphotyrosine picked threonine kinase, sgc, structural genomics consortium, atp-binding, nucleotide-binding, phosphoprotein, serine/threonine-protein kinase, transferase, tyrosine-protein kinase |
| Biological source | Homo sapiens (human) |
| Total number of polymer chains | 1 |
| Total formula weight | 36736.03 |
| Authors | Filippakopoulos, P.,Soundararajan, M.,Keates, T.,Elkins, J.M.,King, O.,Fedorov, O.,Picaud, S.S.,Pike, A.C.W.,Roos, A.,Pilka, E.,von Delft, F.,Arrowsmith, C.H.,Edwards, A.M.,Weigelt, J.,Bountra, C.,Knapp, S.,Structural Genomics Consortium (SGC) (deposition date: 2008-02-29, release date: 2008-03-18, Last modification date: 2023-08-30) |
| Primary citation | Kwiatkowski, N.,Jelluma, N.,Filippakopoulos, P.,Soundararajan, M.,Manak, M.S.,Kwon, M.,Choi, H.G.,Sim, T.,Deveraux, Q.L.,Rottmann, S.,Pellman, D.,Shah, J.V.,Kops, G.J.,Knapp, S.,Gray, N.S. Small-molecule kinase inhibitors provide insight into Mps1 cell cycle function. Nat.Chem.Biol., 6:359-368, 2010 Cited by PubMed Abstract: 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. PubMed: 20383151DOI: 10.1038/nchembio.345 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.3 Å) |
Structure validation
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