3GFW

Crystal Structure of Human Dual Specificity Protein Kinase (TTK) in complex with a pyrolo-pyridin ligand

3GFW の概要

• エントリーDOI: 10.2210/pdb3gfw/pdb
• 分子名称: Dual specificity protein kinase TTK, 1-(4-(4-(2-(isopropylsulfonyl)phenylamino)-1H-pyrrolo[2,3-b]pyridin-6-ylamino)-3-methoxyphenyl)piperidin-4-ol, 2-(2-(2-(2-(2-(2-ETHOXYETHOXY)ETHOXY)ETHOXY)ETHOXY)ETHOXY)ETHANOL, ... (4 entities in total)
• 機能のキーワード: 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
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 37271.68

構造登録者

Filippakopoulos, P.,Soundararajan, M.,Choi, H.,Keates, T.,Elkins, J.M.,King, O.,Fedorov, O.,Picaud, S.S.,Pike, A.C.W.,von Delft, F.,Arrowsmith, C.H.,Edwards, A.,Weigelt, J.,Bountra, C.,Grey, N.,Knapp, S.,Structural Genomics Consortium (SGC) (登録日: 2009-02-27, 公開日: 2009-03-17, 最終更新日: 2023-09-06)

主引用文献

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

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: 20383151
DOI: 10.1038/nchembio.345

実験手法

X-RAY DIFFRACTION (2.74 Å)