2X0Y

Screening-based discovery of drug-like O-GlcNAcase inhibitor scaffolds

2X0Y の概要

• エントリーDOI: 10.2210/pdb2x0y/pdb
• 関連するPDBエントリー: 2CBI 2CBJ 2J62 2JH2 2V5C 2V5D 2VUR 2WB5
• 分子名称: O-GLCNACASE NAGJ, 7-[(2S)-2,3-DIHYDROXYPROPYL]-1,3-DIMETHYL-3,7-DIHYDRO-1H-PURINE-2,6-DIONE (3 entities in total)
• 機能のキーワード: glycosidase, hydrolase, cell adhesion
• 由来する生物種: CLOSTRIDIUM PERFRINGENS
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 133885.91

構造登録者

Dorfmueller, H.C.,van Aalten, D.M.F. (登録日: 2009-12-18, 公開日: 2010-01-12, 最終更新日: 2023-12-20)

主引用文献

Dorfmueller, H.C.,Van Aalten, D.M.F.
Screening-Based Discovery of Drug-Like O-Glcnacase Inhibitor Scaffolds
FEBS Lett., 584:694-, 2010

PubMed Abstract: O-GlcNAcylation is an essential posttranslational modification in metazoa. Modulation of O-GlcNAc levels with small molecule inhibitors of O-GlcNAc hydrolase (OGA) is a useful strategy to probe the role of this modification in a range of cellular processes. Here we report the discovery of novel, low molecular weight and drug-like O-GlcNAcase inhibitor scaffolds by high-throughput screening. Kinetic and X-ray crystallographic analyses of the binding modes with human/bacterial O-GlcNAcases identify some of these as competitive inhibitors. Comparative kinetic experiments with the mechanistically related human lysosomal hexosaminidases reveal that three of the inhibitor scaffolds show selectivity towards human OGA. These scaffolds provide attractive starting points for the development of non-carbohydrate, drug-like OGA inhibitors.

PubMed: 20026047
DOI: 10.1016/J.FEBSLET.2009.12.020

実験手法

X-RAY DIFFRACTION (2.25 Å)