2YCS

Crystal structure of checkpoint kinase 2 in complex with PV788

2YCS の概要

• エントリーDOI: 10.2210/pdb2ycs/pdb
• 関連するPDBエントリー: 1GXC 2CN5 2CN8 2W0J 2W7X 2WTC 2WTD 2WTI 2WTJ 2XBJ 2XM8 2XM9 2YCF 2YCQ 2YCR
• 分子名称: SERINE/THREONINE-PROTEIN KINASE CHK2, N-{4-[(1E)-N-CARBAMIMIDOYLETHANEHYDRAZONOYL]PHENYL}-1H-INDOLE-3-CARBOXAMIDE, NITRATE ION, ... (4 entities in total)
• 機能のキーワード: transferase, anticancer drug design
• 由来する生物種: HOMO SAPIENS (HUMAN)
• 細胞内の位置: Isoform 2: Nucleus. Isoform 4: Nucleus. Isoform 7: Nucleus. Isoform 9: Nucleus. Isoform 12: Nucleus. Nucleus, PML body: O96017
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 36958.62

構造登録者

Lountos, G.T.,Jobson, A.G.,Tropea, J.E.,Self, C.R.,Pommier, Y.,Shoemaker, R.H.,Zhang, G.,Waugh, D.S. (登録日: 2011-03-16, 公開日: 2011-11-16, 最終更新日: 2023-12-20)

主引用文献

Lountos, G.T.,Jobson, A.G.,Tropea, J.E.,Self, C.R.,Zhang, G.,Pommier, Y.,Shoemaker, R.H.,Waugh, D.S.
Structural Characterization of Inhibitor Complexes with Checkpoint Kinase 2 (Chk2), a Drug Target for Cancer Therapy.
J.Struct.Biol., 176:292-, 2011

PubMed Abstract: Chk2 (checkpoint kinase 2) is a serine/threonine kinase that participates in a series of signaling networks responsible for maintaining genomic integrity and responding to DNA damage. The development of selective Chk2 inhibitors has recently attracted much interest as a means of sensitizing cancer cells to current DNA-damaging agents used in the treatment of cancer. Additionally, selective Chk2 inhibitors may reduce p53-mediated apoptosis in normal tissues, thereby helping to mitigate adverse side effects from chemotherapy and radiation. Thus far, relatively few selective inhibitors of Chk2 have been described and none have yet progressed into clinical trials. Here, we report crystal structures of the catalytic domain of Chk2 in complex with a novel series of potent and selective small molecule inhibitors. These compounds exhibit nanomolar potencies and are selective for Chk2 over Chk1. The structures reported here elucidate the binding modes of these inhibitors to Chk2 and provide information that can be exploited for the structure-assisted design of novel chemotherapeutics.

PubMed: 21963792
DOI: 10.1016/J.JSB.2011.09.008

実験手法

X-RAY DIFFRACTION (2.35 Å)