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Forschungsdatenbank PMU-SQQUID

A novel FRET peptide assay reveals efficient Helicobacter pylori HtrA inhibition through zinc and copper binding.
Bernegger, S; Brunner, C; Vizovišek, M; Fonovic, M; Cuciniello, G; Giordano, F; Stanojlovic, V; Jarzab, M; Simister, P; Feller, SM; Obermeyer, G; Posselt, G; Turk, B; Cabrele, C; Schneider, G; Wessler, S;
Sci Rep. 2020; 10(1):10563
Originalarbeiten (Zeitschrift)

PMU-Autor/inn/en

Bernegger Sabine

Abstract

Helicobacter pylori (H. pylori) secretes the chaperone and serine protease high temperature requirement A (HtrA) that cleaves gastric epithelial cell surface proteins to disrupt the epithelial integrity and barrier function. First inhibitory lead structures have demonstrated the essential role of HtrA in H. pylori physiology and pathogenesis. Comprehensive drug discovery techniques allowing high-throughput screening are now required to develop effective compounds. Here, we designed a novel fluorescence resonance energy transfer (FRET) peptide derived from a gel-based label-free proteomic approach (direct in-gel profiling of protease specificity) as a valuable substrate for H. pylori HtrA. Since serine proteases are often sensitive to metal ions, we investigated the influence of different divalent ions on the activity of HtrA. We identified Zn


Useful keywords (using NLM MeSH Indexing)

Bacterial Proteins/antagonists*

inhibitors*

Bacterial Proteins/metabolism

Cadherins/metabolism

Copper/metabolism

Drug Evaluation, Preclinical/methods*

Fluorescence Resonance Energy Transfer/methods*

Helicobacter Infections/drug therapy

Helicobacter Infections/metabolism

Helicobacter pylori/metabolism

Molecular Chaperones/metabolism

Peptides/metabolism

Proteomics/methods

Serine Endopeptidases/metabolism

Serine Proteases/metabolism

Zinc/metabolism