Alpha-1 antitrypsin inhibits Clostridium botulinum C2 toxin, Corynebacterium diphtheriae diphtheria toxin and B. anthracis fusion toxin.
Clostridium botulinum C2 toxin
Anthrax toxin
Diphtheria toxin
Drug repurposing
Toxin inhibitor
α1-Antitrypsin
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
11 Sep 2024
11 Sep 2024
Historique:
received:
19
06
2024
accepted:
30
08
2024
medline:
12
9
2024
pubmed:
12
9
2024
entrez:
11
9
2024
Statut:
epublish
Résumé
The bacterium Clostridium botulinum, well-known for producing botulinum neurotoxins, which cause the severe paralytic illness known as botulism, produces C2 toxin, a binary AB-toxin with ADP-ribosyltranferase activity. C2 toxin possesses two separate protein components, an enzymatically active A-component C2I and the binding and translocation B-component C2II. After proteolytic activation of C2II to C2IIa, the heptameric structure binds C2I and is taken up via receptor-mediated endocytosis into the target cells. Due to acidification of endosomes, the C2IIa/C2I complex undergoes conformational changes and consequently C2IIa forms a pore into the endosomal membrane and C2I can translocate into the cytoplasm, where it ADP-ribosylates G-actin, a key component of the cytoskeleton. This modification disrupts the actin cytoskeleton, resulting in the collapse of cytoskeleton and ultimately cell death. Here, we show that the serine-protease inhibitor α
Identifiants
pubmed: 39261531
doi: 10.1038/s41598-024-71706-7
pii: 10.1038/s41598-024-71706-7
doi:
Substances chimiques
Botulinum Toxins
EC 3.4.24.69
botulinum toxin type C
FPM7829VMX
alpha 1-Antitrypsin
0
Bacterial Toxins
0
Diphtheria Toxin
0
Antigens, Bacterial
0
anthrax toxin
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
21257Subventions
Organisme : Deutsche Forschungsgemeinschaft
ID : 316249678-SFB1279
Organisme : Deutsche Forschungsgemeinschaft
ID : 316249678-SFB1279
Informations de copyright
© 2024. The Author(s).
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