Related Experiment Video
Updated: Oct 3, 2026

Method for Identifying Small Molecule Inhibitors of the Protein-protein Interaction Between HCN1 and TRIP8b
Published on: November 11, 2016
Identification of an inhibitor of hsc70-mediated protein translocation and ATP hydrolysis
S W Fewell1, B W Day, J L Brodsky
1Department of Biological Sciences, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, USA.
Abstract:
Members of the hsc70 family of molecular chaperones are critical players in the folding and quality control of cellular proteins. Because several human diseases arise from defects in protein folding, the activity of hsc70 chaperones is a potential therapeutic target for these disorders. By using a known hsc70 modulator, 15-deoxyspergualin, as a seed, we identified a novel inhibitor of hsc70 activity. This compound, R/1, inhibits the endogenous and DnaJ-stimulated ATPase activity of hsc70 by 48 and 51%, respectively, and blocks the hsc70-mediated translocation of a preprotein into yeast endoplasmic reticulum-derived microsomal vesicles. Biochemical studies demonstrate that R/1 most likely exerts these effects by altering the oligomeric state of hsc70.
Related Concept Videos
The Electron Transport Chain
Inhibitors of the electron transport chain
Rotenone, a widely used pesticide, prevents electron transfer from Fe-S cluster to ubiquinone or Q in...
Destabilization of Microtubules
Energy to Drive Translocation
Generally, polypeptides are unfolded by two distinct...
Allosteric Proteins-ATCase
Aspartate transcarbamoylase (ATCase) is a cytosolic enzyme that catalyzes the condensation of L-aspartate and carbamoyl phosphate to N-carbamoyl-L-aspartate. This reaction is the first step in pyrimidine biosynthesis. UTP and CTP, the end products of the pyrimidine synthesis pathway,...

