Abstract 1571 Structure and mechanism of novel allosteric inhibitors of Human ClpP protease
Objective: To characterize two novel inhibitory mechanisms that leverage allosteric hotspots of human ClpP, a cancer therapeutic target. Human ClpP is a mitochondrial protease and a cancer therapeutic target. As such, there is major interest in the development of potent and specific small-molecule drugs that target ClpP. ClpP exists as heptamers and tetradecamers. The transition between oligomeric states is mediated by the handle domain, a strand-turn-helix motif that interlocks two heptameric rings.
Authors
- Algirdas Vėlyvis (ORCID: https://orcid.org/0009-0007-1774-3088)
- Monica M. Goncalves (ORCID: https://orcid.org/0009-0001-2447-146X)
- Rima Al‐awar (ORCID: https://orcid.org/0000-0002-4185-055X)
- Natalie Zeytuni (ORCID: https://orcid.org/0000-0002-5708-4095)
- Aaron David Schimmer (ORCID: https://orcid.org/0000-0003-4023-3899)
- Iain Watson (ORCID: https://orcid.org/0000-0002-0673-2718)
- Siavash Vahidi (ORCID: https://orcid.org/0000-0001-8637-3710)
- Adwaith B. Uday (ORCID: https://orcid.org/0009-0005-1524-6307)
- Stefan Currie (ORCID: https://orcid.org/0009-0000-9652-6901)
Institutions
- University of Guelph (CA)
Publication Details
- Journal
- Journal of Biological Chemistry
- Published
- 2025-05-01
- DOI
- https://doi.org/10.1016/j.jbc.2025.109901
- Primary Topic
- Click Chemistry and Applications
- Type
- article
- Field-Weighted Citation Impact
- 0.00