Publications by authors named "Chethan K Krishna"
Quantum mechanics-driven structure-activity relationship study of PEX5-PEX14 protein-protein interaction inhibitors based on a dibenzo[b,e]azepin-6(6H)-one scaffold.
Eur J Med Chem
November 2025
Targeting protein-protein interactions (PPIs) is a promising strategy in drug development. However, despite the considerable progress in the field, targeting PPIs with small molecules remains challenging, requiring novel strategies in inhibitor design and subsequent structure-activity relationship (SAR) studies. We have recently identified the PEX5-PEX14 PPI as a novel therapeutic target against diseases related to Trypanosoma infections and discovered small-molecule inhibitors against PEX14 using structure-based drug discovery (SBDD).
View Article and Find Full Text PDFTrypanosomatid parasite infections cause Chagas disease, human African trypanosomiasis, and leishmaniasis, affecting over 12 million people worldwide. Glycosomes, the peroxisome-related organelles of trypanosomes, are essential for survival, making their metabolic functions and biogenesis mediated by peroxins (PEXs) suitable drug targets. We report a comprehensive protein inventory of glycosomal membranes, defined through advanced subcellular membrane protein profiling combined with quantitative mass spectrometry and including 28 high-confidence glycosomal membrane proteins.
View Article and Find Full Text PDFArticle Synopsis
- PEX19 binding sites are crucial for the proper targeting and localization of PEX11, a key peroxisomal and glycosomal membrane protein.
- There are two main PEX19 binding sites in PEX11, with the N-terminal site being highly conserved and necessary for its effective targeting, while the second site promotes glycosomal localization.
- Mutations or deletions in these binding sites can cause mislocalization of PEX11 to mitochondria, and the N-terminal region of PEX11 harbors a signal that redirects it to mitochondria when glycosomal transport is impaired.
Article Synopsis
- * Since glycosomes are unique to these parasites, they are of significant interest for research in parasite biology and potential treatments.
- * The text outlines a method for isolating highly purified glycosomes and enriching their membrane proteins from the Trypanosoma brucei, involving techniques like cell rupture, differential centrifugation, and various buffer extractions.