7PA3

PARK7 with covalent inhibitor JYQ-88

This is a non-PDB format compatible entry.

Summary for 7PA3

• Entry DOI: 10.2210/pdb7pa3/pdb
• Descriptor: Parkinson disease protein 7, (3~{S})-~{N}-[5-[2-[(azanylidene-$l^{4}-azanylidene)amino]ethanoyl]-6,7-dihydro-4~{H}-[1,3]thiazolo[5,4-c]pyridin-2-yl]-1-(iminomethyl)pyrrolidine-3-carboxamide (3 entities in total)
• Functional Keywords: deglycase, inhibitor, unknown function
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 1
• Total formula weight: 20495.72

Authors

Kim, R.Q.,Jia, Y.,Sapmaz, A.,Geurink, P.P. (deposition date: 2021-07-28, release date: 2022-08-10, Last modification date: 2024-10-23)

Primary citation

Jia, Y.,Kim, R.Q.,Kooij, R.,Ovaa, H.,Sapmaz, A.,Geurink, P.P.
Chemical Toolkit for PARK7: Potent, Selective, and High-Throughput.
J.Med.Chem., 65:13288-13304, 2022

PubMed Abstract: The multifunctional human Parkinson's disease protein 7 (PARK7/DJ1) is an attractive therapeutic target due to its link with early-onset Parkinson's disease, upregulation in various cancers, and contribution to chemoresistance. However, only a few compounds have been identified to bind PARK7 due to the lack of a dedicated chemical toolbox. We report the creation of such a toolbox and showcase the application of each of its components. The selective PARK7 submicromolar inhibitor with a cyanimide reactive group covalently modifies the active site Cys106. Installment of different dyes onto the inhibitor delivered two PARK7 probes. The Rhodamine110 probe provides a high-throughput screening compatible FP assay, showcased by screening a compound library (8000 molecules). The SulfoCy5-equipped probe is a valuable tool to assess the effect of PARK7 inhibitors in a cell lysate. Our work creates new possibilities to explore PARK7 function in a physiologically relevant setting and develop new and improved PARK7 inhibitors.

PubMed: 36149939
DOI: 10.1021/acs.jmedchem.2c01113

Experimental method

X-RAY DIFFRACTION (1.42 Å)