9F98

Crystal structure of MUS81-EME1, apo form.

9F98 の概要

• エントリーDOI: 10.2210/pdb9f98/pdb
• 分子名称: Crossover junction endonuclease MUS81, Crossover junction endonuclease EME1 (3 entities in total)
• 機能のキーワード: mus81-eme1, fragment, inhibitor, hydrolase
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 140608.17

構造登録者

Collie, G.W. (登録日: 2024-05-07, 公開日: 2024-07-03, 最終更新日: 2024-07-31)

主引用文献

Collie, G.W.,Borjesson, U.,Chen, Y.,Dong, Z.,Di Fruscia, P.,Gohlke, A.,Hoyle, A.,Hunt, T.A.,Jesani, M.H.,Luo, H.,Luptak, J.,Milbradt, A.G.,Narasimhan, P.,Packer, M.,Patel, S.,Qiao, J.,Storer, R.I.,Stubbs, C.J.,Tart, J.,Truman, C.,Wang, A.T.,Wheeler, M.G.,Winter-Holt, J.
Fragment-Based Discovery of Novel MUS81 Inhibitors.
Acs Med.Chem.Lett., 15:1151-1158, 2024

PubMed Abstract: MUS81 is a structure-selective endonuclease that cleaves various branched DNA structures arising from natural physiological processes such as homologous recombination and mitosis. Due to this, MUS81 is able to relieve replication stress, and its function has been reported to be critical to the survival of many cancers, particularly those with dysfunctional DNA-repair machinery. There is therefore interest in MUS81 as a cancer drug target, yet there are currently few small molecule inhibitors of this enzyme reported, and no liganded crystal structures are available to guide hit optimization. Here we report the fragment-based discovery of novel small molecule MUS81 inhibitors with sub-μM biochemical activity. These inhibitors were used to develop a novel crystal system, providing the first structural insight into the inhibition of MUS81 with small molecules.

PubMed: 39015284
DOI: 10.1021/acsmedchemlett.3c00453

実験手法

X-RAY DIFFRACTION (2.15 Å)