4C13

x-ray crystal structure of Staphylococcus aureus MurE with UDP-MurNAc- Ala-Glu-Lys

4C13 の概要

• エントリーDOI: 10.2210/pdb4c13/pdb
• 関連するPDBエントリー: 4C12
• 関連するBIRD辞書のPRD_ID: PRD_002099
• 分子名称: UDP-N-ACETYLMURAMOYL-L-ALANYL-D-GLUTAMATE--L-LYSINE LIGASE, CHLORIDE ION, MAGNESIUM ION, ... (7 entities in total)
• 機能のキーワード: ligase, mure
• 由来する生物種: STAPHYLOCOCCUS AUREUS
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 56508.38

構造登録者

Ruane, K.M.,Roper, D.I.,Fulop, V.,Barreteau, H.,Boniface, A.,Dementin, S.,Blanot, D.,Mengin-Lecreulx, D.,Gobec, S.,Dessen, A.,Dowson, C.G.,Lloyd, A.J. (登録日: 2013-08-09, 公開日: 2013-10-02, 最終更新日: 2025-04-09)

主引用文献

Wang, L.,Shao, X.,Zhong, T.,Wu, Y.,Xu, A.,Sun, X.,Gao, H.,Liu, Y.,Lan, T.,Tong, Y.,Tao, X.,Du, W.,Wang, W.,Chen, Y.,Li, T.,Meng, X.,Deng, H.,Yang, B.,He, Q.,Ying, M.,Rao, Y.
Discovery of a first-in-class CDK2 selective degrader for AML differentiation therapy.
Nat.Chem.Biol., 2021

PubMed Abstract: The discovery of effective therapeutic treatments for cancer via cell differentiation instead of antiproliferation remains a great challenge. Cyclin-dependent kinase 2 (CDK2) inactivation, which overcomes the differentiation arrest of acute myeloid leukemia (AML) cells, may be a promising method for AML treatment. However, there is no available selective CDK2 inhibitor. More importantly, the inhibition of only the enzymatic function of CDK2 would be insufficient to promote notable AML differentiation. To further validate the role and druggability of CDK2 involved in AML differentiation, a suitable chemical tool is needed. Therefore, we developed first-in-class CDK2-targeted proteolysis-targeting chimeras (PROTACs), which promoted rapid and potent CDK2 degradation in different cell lines without comparable degradation of other targets, and induced remarkable differentiation of AML cell lines and primary patient cells. These data clearly demonstrated the practicality and importance of PROTACs as alternative tools for verifying CDK2 protein functions.

PubMed: 33664520
DOI: 10.1038/s41589-021-00742-5

実験手法

X-RAY DIFFRACTION (1.9 Å)