E. coli heat-labile enterotoxin

FIG. 30. The best ligands against E. coli heat-labile enterotoxin. 

J. C. Pickens, E. A. Merritt, M. Ahn, C. L. M. J. Verlinde, W. G. J. Hoi, and E. Fan, Anchor-based design of improved cholera toxin and E. coli heat-labile enterotoxin receptor binding antagonists that display multiple binding modes, Chem. Biol., 9 (2002) 215-224. 

Merritt EA, Pronk SE, Sixmo TK, et al. (1994a) Structure of partially-activated E. coli heat-labile enterotoxin (LT) at 2.6 A resolution. In FEBS Let. 337 88-92. 

Cholera toxin (CT) and E. coli heat-labile enterotoxin (LT-1 or LT) are members of the AB5 family of ADP-ribosylating toxins (Merritt and Hoi,... 

The mono(ADP-ribosyl)ation, the transfer of the ADP-ribose moiety of NAD to a macromolecule, was discovered by Hayaishi et al. in 1968 as the mechanism of the cytotoxic effect of diphtheria toxin [1], The substrate of this toxin-catalyzed ADP-ribosylation is elongation factor-2. The same reaction is catal)Azed by Pseudomonas toxin. The second bacterial toxin involved in mono(ADP-ribosyl)ation of mammalian cell proteins is cholera toxin, the substrate of which was identified as the guanine nucleotide-binding regulatory component of membrane adenylate cyclase in 1978 [2].E. coli heat-labile enterotoxin is similar to cholera toxin in many respects. 

The structure of E.coli heat-labile enterotoxin determined by X-ray crystallography and downloaded from the Protein Data Bank (see page 700). The protein has seven subunits—that is seven protein chains (Section 22.16). Five of them (blue, green purple, etc.) attach to a cell membrane. The toxin uses the red helical spike to deliver the catalytic subunit (orange) into the cell. The red and gray space-filling model is a protein side chain that acts as a base catalyst (Section 23.9). This toxin is responsible for what is known as traveler s diarrhea. 

Spangler B.D., Wilkinson E.A., Murphyb J.T., Tyler B.J., Comparison of the Spreeta surface plasmon resonance sensor and a quartz crystal microbalance for detection of Escherichia coli heat-labile enterotoxins, Analytica Chimica Acta 2001 444 149-161. 

Tamura S, Hatori E, Tsuruhara T et al. Suppression of delayed-type hypersensitivity and IgE antibody responses to ovalbumin by intranasal administration of Escherichia coli heat-labile enterotoxin B subunit-conjugated ovalbumin. Vaccine 1997 15(2) 225-229. 

Loregian A, Papini E, Satin B et al. Intranuclear delivery of an antiviral peptide mediated by the B subunit of Escherichia coli heat-labile enterotoxin. Proc Natl Acad Sci USA 1999 96(9) 5221-5226. 

J. P. Thompson and C.-L. Schengrund, Oligosaccharide-derivatized dendrimers Defined multivalent inhibitors of the adherence of the cholera toxin B subunit and the heat labile enterotoxin of E. coli to GM1, Glycoconjug. J., 14 (1997) 837-845. 

E. coli B subunit of the heat labile enterotoxin (LTB) fused to an immu-nocontraceptive epitope Tomato fruit and leaves No immunogenicity assays performed. 91... 

There are a large number of proteins that share this designation. Perhaps the best known is the heat-labile enterotoxin from E. coli that catalyzes the ADP-ribosyla-tion of a number of proteins. 

Ryan, E.T. Crean, T.I. John, M. Butterton, J.R. Clements, J.D. Calderwood, S.B. Vivo expression and immunoadjuvancy of a mutant of heat-labile enterotoxin of escherichia coli in vaccine and vector strains of vibrio cholerae. Infect. Immun. 1999, 67, 1694—1701. 

Cholera toxin and the very similar (in structure and mechanism of action) heat-labile enterotoxin from E. coli (LT-1 or LT, which is responsible for the syndrome of traveler s diarrhea) have been widely applied as molecular tools to facilitate understanding of signalling systems. Examples of molecules besides Gs that were identified because of work on CT are the ADP-ribosylation factors (ARFs), now known to play a critical role in intracellular vesicular transport (Moss and Vaughan, 1995), and the mammalian ADP-ribosyltransferases (Zolkiewska et al., 1994). As more is learned about CT structure and biochemistry, modified or mutant CT and LT molecules are being gen-... 

The heat-labile E. coli enterotoxin, whose gene is carried on a plasmid, is a close relative of cholera toxin11 0 and also catalyzes ADP ribosylation of arginine 201 of the Gsa subunit.111 Bordetella pertussis, which causes whooping cough, forms a similar toxin that attacks the inhibitory regulatory protein G v as well as transducin and inactivates them by ADP ribosylation. Diphtheria toxin (Box 29-A), the exotoxin from Pseudomonas aeruginosa, and the toxin from Clostridium botulinum also catalyze ADP-ribosylation reactions.k/1 ... 

Several E. coli strains also elaborate heat-labile entero-toxins that cause diarrheal disease ( traveller s diarrhea) by similar mechanisms. In V. cholerae, the same enterotoxin is produced by all pathogenic strains and is chro-mosomally determined, whereas in E. coli, different en-terotoxins are produced and the toxin genes are carried on plasmids. 

Enterotoxigenic E. coli are capable of producing two plasmid-mediated enterotoxins heat-labile toxin (HLT) and heat-stable toxin (HST)." A cholera-like toxin, HLT has two subunits (A and B) that... 

The heat-labile toxin B subunit of E. coli (LTB) [398], hepatitis B surface antigen [404], respiratory syncytial virus F protein [258], measles virus hemagglutinin [180], and Norwalk virus capsid protein [240, 405, 406] have each been successfully expressed in plants and delivered orally in animals or humans to determine their im-munoprophylactic activity. The first account of a human clinical trial of oral vaccine based on an E. coli enterotoxin as... 

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