scholarly journals Human α-defensins neutralize toxins of the mono-ADP-ribosyltransferase family

2006 ◽  
Vol 399 (2) ◽  
pp. 225-229 ◽  
Author(s):  
Chun Kim ◽  
Zoya Slavinskaya ◽  
A. Rod Merrill ◽  
Stefan H. E. Kaufmann
Keyword(s):  
Human Neutrophil ◽  
Biological Function ◽  
Elongation Factor ◽  
Bacterial Toxin ◽  
Pseudomonas Exotoxin ◽  
Pseudomonas Exotoxin A ◽  
Elongation Factor 2 ◽  
Eukaryotic Elongation Factor 2 ◽  
Eukaryotic Elongation Factor ◽  
Adp Ribosyltransferase

Various bacterial pathogens secrete toxins, which are not only responsible for fatal pathogenesis of disease, but also facilitate evasion of host defences. One of the best-known bacterial toxin groups is the mono-ADP-ribosyltransferase family. In the present study, we demonstrate that human neutrophil α-defensins are potent inhibitors of the bacterial enzymes, particularly against DT (diphtheria toxin) and ETA (Pseudomonas exotoxin A). HNP1 (human neutrophil protein 1) inhibited DT- or ETA-mediated ADP-ribosylation of eEF2 (eukaryotic elongation factor 2) and protected HeLa cells against DT- or ETA-induced cell death. Kinetic analysis revealed that inhibition of DT and ETA by HNP1 was competitive with respect to eEF2 and uncompetitive against NAD+ substrates. Our results reveal that toxin neutralization represents a novel biological function of HNPs in host defence.

scholarly journals Crystal Structure of Exotoxin A from Aeromonas Pathogenic Species

Toxins ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 397 ◽  
Author(s):  
Geoffrey Masuyer
Keyword(s):  
Crystal Structure ◽  
Metal Binding ◽  
Elongation Factor ◽  
Pathogenic Species ◽  
Exotoxin A ◽  
Pseudomonas Exotoxin A ◽  
Eukaryotic Elongation Factor 2 ◽  
Eukaryotic Elongation Factor ◽  
Bacterial Virulence Factor ◽  
Interdomain Interactions

Aeromonas exotoxin A (AE) is a bacterial virulence factor recently discovered in a clinical case of necrotising fasciitis caused by the flesh-eating Aeromonas hydrophila. Here, database mining shows that AE is present in the genome of several emerging Aeromonas pathogenic species. The X-ray crystal structure of AE was solved at 2.3 Å and presents all the hallmarks common to diphthamide-specific mono-ADP-ribosylating toxins, suggesting AE is a fourth member of this family alongside the diphtheria toxin, Pseudomonas exotoxin A and cholix. Structural homology indicates AE may use a similar mechanism of cytotoxicity that targets eukaryotic elongation factor 2 and thus inhibition of protein synthesis. The structure of AE also highlights unique features including a metal binding site, and a negatively charged cleft that could play a role in interdomain interactions and may affect toxicity. This study raises new opportunities to engineer alternative toxin-based molecules with pharmaceutical potential.

scholarly journals Chaperone Function of Hgh1 in the Biogenesis of Eukaryotic Elongation Factor 2

2019 ◽  
Vol 74 (1) ◽  
pp. 88-100.e9 ◽  
Author(s):  
Leonie Mönkemeyer ◽  
Courtney L. Klaips ◽  
David Balchin ◽  
Roman Körner ◽  
F. Ulrich Hartl ◽  
...  
Keyword(s):  
Elongation Factor ◽  
Chaperone Function ◽  
Elongation Factor 2 ◽  
Eukaryotic Elongation Factor 2 ◽  
Eukaryotic Elongation Factor
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