A novel FRET peptide assay reveals efficient Helicobacter pylori HtrA inhibition through zinc and copper binding.
Bacterial Proteins
/ antagonists & inhibitors
Cadherins
/ metabolism
Copper
/ metabolism
Drug Evaluation, Preclinical
/ methods
Fluorescence Resonance Energy Transfer
/ methods
Helicobacter Infections
/ drug therapy
Helicobacter pylori
/ metabolism
Molecular Chaperones
/ metabolism
Peptides
/ metabolism
Proteomics
/ methods
Serine Endopeptidases
/ metabolism
Serine Proteases
/ metabolism
Zinc
/ metabolism
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
29 06 2020
29 06 2020
Historique:
received:
21
12
2019
accepted:
09
06
2020
entrez:
1
7
2020
pubmed:
1
7
2020
medline:
16
1
2021
Statut:
epublish
Résumé
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
Identifiants
pubmed: 32601479
doi: 10.1038/s41598-020-67578-2
pii: 10.1038/s41598-020-67578-2
pmc: PMC7324608
doi:
Substances chimiques
Bacterial Proteins
0
Cadherins
0
Molecular Chaperones
0
Peptides
0
Copper
789U1901C5
HtrA protein, H pylori
EC 3.4.-
Serine Proteases
EC 3.4.-
Serine Endopeptidases
EC 3.4.21.-
Zinc
J41CSQ7QDS
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
10563Subventions
Organisme : Austrian Science Fund FWF
ID : P_31507
Pays : Austria
Organisme : Austrian Science Fund FWF
ID : I_4360
Pays : Austria
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