{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Tashiro S"],"funding":["NIGMS NIH HHS"],"pagination":["2783-2793"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC6370461"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["13(9)"],"pubmed_abstract":["DJ-1 is a Parkinson's disease associated protein endowed with enzymatic, redox sensing, regulatory, chaperoning, and neuroprotective activities. Although DJ-1 has been vigorously studied for the past decade and a half, its exact role in the progression of the disease remains uncertain. In addition, little is known about the spatiotemporal regulation of DJ-1, or the biochemical basis explaining its numerous biological functions. Progress has been hampered by the lack of inhibitors with precisely known mechanisms of action. Herein, we have employed biophysical methodologies and X-ray crystallography to identify and to optimize a family of compounds inactivating the critical Cys106 residue of human DJ-1. We demonstrate these compounds are potent inhibitors of various activities of DJ-1 in vitro and in cell-based assays. This study reports a new family of DJ-1 inhibitors with a defined mechanism of action, and contributes toward the understanding of the biological function of DJ-1."],"journal":["ACS chemical biology"],"pubmed_title":["Discovery and Optimization of Inhibitors of the Parkinson's Disease Associated Protein DJ-1."],"pmcid":["PMC6370461"],"funding_grant_id":["R01 GM111639","R01 GM115844"],"pubmed_authors":["Caaveiro JMM","Nagatoishi S","Hoang QQ","Tamura Y","Nakakido M","Tsumoto K","Matsuda N","Liu D","Tanabe A","Tashiro S"],"additional_accession":[]},"is_claimable":false,"name":"Discovery and Optimization of Inhibitors of the Parkinson's Disease Associated Protein DJ-1.","description":"DJ-1 is a Parkinson's disease associated protein endowed with enzymatic, redox sensing, regulatory, chaperoning, and neuroprotective activities. Although DJ-1 has been vigorously studied for the past decade and a half, its exact role in the progression of the disease remains uncertain. In addition, little is known about the spatiotemporal regulation of DJ-1, or the biochemical basis explaining its numerous biological functions. Progress has been hampered by the lack of inhibitors with precisely known mechanisms of action. Herein, we have employed biophysical methodologies and X-ray crystallography to identify and to optimize a family of compounds inactivating the critical Cys106 residue of human DJ-1. We demonstrate these compounds are potent inhibitors of various activities of DJ-1 in vitro and in cell-based assays. This study reports a new family of DJ-1 inhibitors with a defined mechanism of action, and contributes toward the understanding of the biological function of DJ-1.","dates":{"release":"2018-01-01T00:00:00Z","publication":"2018 Sep","modification":"2021-02-20T01:04:48Z","creation":"2019-03-26T22:54:23Z"},"accession":"S-EPMC6370461","cross_references":{"pubmed":["30063823"],"doi":["10.1021/acschembio.8b00701"]}}