Structural Dynamics of the Ubiquitin Specific Protease USP30 in Complex with a Cyanopyrrolidine-Containing Covalent Inhibitor
Darragh P O’Brien,
Hannah BL Jones,
Yuqi Shi
et al.
Abstract:Inhibition of the mitochondrial deubiquitinating enzyme USP30 is neuroprotective and presents therapeutic opportunities for the treatment of idiopathic Parkinson’s Disease and mitophagy-related disorders. We have integrated structural and quantitative proteomics with biochemical assays to decipher the mode of action of covalent USP30 inhibition by a small molecule containing a cyanopyrrolidine reactive group,USP30-I-1. The inhibitor demonstrated high potency and selectivity for endogenous USP30 in neuroblastom… Show more
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