6FDK

Structure of Chlamydia trachomatis effector protein Cdu1 bound to ubiquitin

Summary for 6FDK

• Entry DOI: 10.2210/pdb6fdk/pdb
• Related: 5B5Q 5HAG
• Descriptor: Deubiquitinase and deneddylase Dub1, Polyubiquitin-B, CHLORIDE ION, ... (5 entities in total)
• Functional Keywords: chladub1, ce protease, dub, ubiquitin., hydrolase
• Biological source: Chlamydia trachomatis 434/Bu; More
• Total number of polymer chains: 2
• Total formula weight: 39066.49

Authors

Ramirez, Y.,Kisker, C. (deposition date: 2017-12-25, release date: 2018-08-15, Last modification date: 2024-02-07)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (1.6 Å)