TARGETING MITOCHONDRIAL DAMAGE REPAIR
Novel anticancer drug design starts with understanding how drug-like agonists bind to their target
Feb. 27, 2023
Maintaining mitochondrial proteins is essential to its function as an energy factory. An intricate protein quality control mechanism helps support the mitochondria to control activity and recycle old or misfolded proteins. Interrupting the protein quality control mechanism is a hallmark of many cancers and attractive target for novel drug design.
Using the CMCF-BM beamline, researchers from the University of Toronto generated structures of a novel class of analogs which bind and activate the protease ClpP.. Analogs with different affinity to ClpP provide a basis for further modification for rational design of novel anticancer drugs.
PDB: 7UVM, 7UVN, 7UVR, 7UVU, 7UW0
Reference: Mabanglo, Mark F., et al. "Potent ClpP agonists with anticancer properties bind with improved structural complementarity and alter the mitochondrial N-terminome." Structure (2022). DOI: https://doi.org/10.1016/j.str.2022.12.002
See also: CLS News