4YUR

Crystal Structure of Plk4 Kinase Domain Bound to Centrinone

4YUR の概要

• エントリーDOI: 10.2210/pdb4yur/pdb
• 分子名称: Serine/threonine-protein kinase PLK4, 2-({2-fluoro-4-[(2-fluoro-3-nitrobenzyl)sulfonyl]phenyl}sulfanyl)-5-methoxy-N-(3-methyl-1H-pyrazol-5-yl)-6-(morpholin-4-yl)pyrimidin-4-amine (3 entities in total)
• 機能のキーワード: transferase, protein kinase, inhibitor, transferase-transferase inhibitor complex, transferase/transferase inhibitor
• 由来する生物種: Homo sapiens (Human)
• 細胞内の位置: Cytoplasm, cytoskeleton, microtubule organizing center, centrosome, centriole: O00444
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 32269.21

構造登録者

Shiau, A.K.,Motamedi, A. (登録日: 2015-03-19, 公開日: 2015-06-17, 最終更新日: 2023-09-27)

主引用文献

Wong, Y.L.,Anzola, J.V.,Davis, R.L.,Yoon, M.,Motamedi, A.,Kroll, A.,Seo, C.P.,Hsia, J.E.,Kim, S.K.,Mitchell, J.W.,Mitchell, B.J.,Desai, A.,Gahman, T.C.,Shiau, A.K.,Oegema, K.
Cell biology. Reversible centriole depletion with an inhibitor of Polo-like kinase 4.
Science, 348:1155-1160, 2015

PubMed Abstract: Centrioles are ancient organelles that build centrosomes, the major microtubule-organizing centers of animal cells. Extra centrosomes are a common feature of cancer cells. To investigate the importance of centrosomes in the proliferation of normal and cancer cells, we developed centrinone, a reversible inhibitor of Polo-like kinase 4 (Plk4), a serine-threonine protein kinase that initiates centriole assembly. Centrinone treatment caused centrosome depletion in human and other vertebrate cells. Centrosome loss irreversibly arrested normal cells in a senescence-like G1 state by a p53-dependent mechanism that was independent of DNA damage, stress, Hippo signaling, extended mitotic duration, or segregation errors. In contrast, cancer cell lines with normal or amplified centrosome numbers could proliferate indefinitely after centrosome loss. Upon centrinone washout, each cancer cell line returned to an intrinsic centrosome number "set point." Thus, cells with cancer-associated mutations fundamentally differ from normal cells in their response to centrosome loss.

PubMed: 25931445
DOI: 10.1126/science.aaa5111

実験手法

X-RAY DIFFRACTION (2.65 Å)