6FDK

Structure of Chlamydia trachomatis effector protein Cdu1 bound to ubiquitin

6FDK の概要

• エントリーDOI: 10.2210/pdb6fdk/pdb
• 関連するPDBエントリー: 5B5Q 5HAG
• 分子名称: Deubiquitinase and deneddylase Dub1, Polyubiquitin-B, CHLORIDE ION, ... (5 entities in total)
• 機能のキーワード: chladub1, ce protease, dub, ubiquitin., hydrolase
• 由来する生物種: Chlamydia trachomatis 434/Bu; 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 39066.49

構造登録者

Ramirez, Y.,Kisker, C. (登録日: 2017-12-25, 公開日: 2018-08-15, 最終更新日: 2024-02-07)

主引用文献

Ramirez, Y.A.,Adler, T.B.,Altmann, E.,Klemm, T.,Tiesmeyer, C.,Sauer, F.,Kathman, S.G.,Statsyuk, A.V.,Sotriffer, C.,Kisker, C.
Structural Basis of Substrate Recognition and Covalent Inhibition of Cdu1 from Chlamydia trachomatis.
ChemMedChem, 13:2014-2023, 2018

PubMed Abstract: Based on the similarity between the active sites of the deubiquitylating and deneddylating enzyme ChlaDub1 (Cdu1) and the evolutionarily related protease adenain, a target-hopping screening approach on a focused set of adenain inhibitors was investigated. The cyanopyrimidine-based inhibitors identified represent the first active-site-directed small-molecule inhibitors of Cdu1. High-resolution crystal structures of Cdu1 in complex with two covalently bound cyanopyrimidines, as well as with its substrate ubiquitin, were obtained. These structural data were complemented by enzymatic assays and covalent docking studies to provide insight into the substrate recognition of Cdu1, active-site pocket flexibility and potential hotspots for ligand interaction. Combined, these data provide a strong basis for future structure-guided medicinal chemistry optimization of this cyanopyrimidine scaffold into more potent and selective Cdu1 inhibitors.

PubMed: 30028574
DOI: 10.1002/cmdc.201800364

実験手法

X-RAY DIFFRACTION (1.6 Å)