Article

Chimeric deubiquitinase engineering reveals structural basis for specific inhibition of USP30 and a framework for DUB ligandability

2024-09-22

Abstract excerpt

The mitochondrial deubiquitinase USP30 negatively regulates Pink1/Parkin-driven mitophagy. Whether enhanced mitochondrial quality control through inhibition of USP30 can protect dopaminergic neurons is currently explored in a clinical trial for Parkinson’s disease. However, the molecular basis for specific inhibition of USP30 by small molecules has remained elusive. Here, we report the crystal structure of human U...

Topics

Open a Topic to create a Post that cites this publication.

Identifiers and source

Literature Corpus work: 178c3290-2e85-5371-b4f3-31965efecb47
DOI: 10.1101/2024.09.22.613429

Open publication

Related research

Semantic proximity does not establish scientific evidence.

Click a neighbor to travelStep 1 · 12 closest

Chimeric deubiquitinase engineering reveals structural basis for specific inhibition of USP30 and a framework for DUB ligandabilityDOI 10.1101/2024.09.22.613429Read

Structural Premise of Selective Deubiquitinase USP30 Inhibition by Small-Molecule BenzosulfonamidesSemantic proximity Read

Assessing the Suitability of Deubiquitylases As Substrates For Targeted Protein DegradationSemantic proximity Read

Molecular Symphony of Mitophagy: Ubiquitin‐Specific Protease‐30 as a Maestro for Precision Management of Neurodegenerative DiseasesSemantic proximity Read

A novel USP30 inhibitor recapitulates genetic loss of USP30 and sets the trigger for PINK1-PARKIN amplification of mitochondrial ubiquitylationSemantic proximity Read

High-content phenotypic screen to identify small molecule enhancers of Parkin-dependent ubiquitination and mitophagy.Semantic proximity Read

Targeting Dual-Impact FBXO7 Mutants Implicated in Parkinson’s Disease and Cancer: An Integrated Approach Using Density Functional Theory, Molecular Docking, and Molecular DynamicsSemantic proximity Read

High-content phenotypic screen to identify small molecule enhancers of Parkin-dependent ubiquitination and mitophagySemantic proximity Read

Structure-based design and characterization of Parkin activating mutationsSemantic proximity Read

Structural basis for regulation of the proteasome 20S core particle by the Parkinsonism-associated proteins FBXO7 and PI31Semantic proximity Read

Benchmarking a highly selective USP30 inhibitor for enhancement of mitophagy and pexophagySemantic proximity Read

Construction of Small-Molecule Deubiquitinase-Targeting Chimeras to Reactivate and Stabilize Mutant p53 Y220C in Vitro and in Vivo.Semantic proximity Read

Investigation of USP30 inhibition to enhance Parkin-mediated mitophagy: tools and approachesSemantic proximity Read