A5047316120- Peptidase Inhibition and Analysis
- Protease and Inhibitor Mechanisms
- Bone Metabolism and Diseases
- Yeasts and Rust Fungi Studies
- Signaling Pathways in Disease
- Galectins and Cancer Biology
- Mycotoxins in Agriculture and Food
- Chemical Synthesis and Analysis
- Biochemical and Structural Characterization
- S100 Proteins and Annexins
- Plant Disease Resistance and Genetics
- Viral Infectious Diseases and Gene Expression in Insects
- Cell Adhesion Molecules Research
Czech Academy of Sciences, Institute of Organic Chemistry and Biochemistry
2018-2022
Charles University
2018-2020
Human cathepsin D (CatD), a pepsin-family aspartic protease, plays an important role in tumor progression and metastasis. Here, we report the development of biomimetic inhibitors CatD as novel tools for regulation this therapeutic target. We designed macrocyclic scaffold to mimic spatial conformation minimal pseudo-dipeptide binding motif pepstatin A, microbial oligopeptide inhibitor, active site. A library more than 30 peptidomimetic was employed optimization, mapping subsite interactions,...
Highlights•New inhibition mechanism revealed in aspartic peptidases (APs)•Oligopeptide inhibitor is proteolytically generated from the AP zymogen•This allosteric binds to an exosite on mature APSummaryPepsin-family are biosynthesized as inactive zymogens which propeptide blocks active site until its proteolytic removal upon enzyme activation. Here, we describe a novel dual regulatory function for using set of crystal structures parasite cathepsin D IrCD1. In IrCD1 zymogen, intramolecular...