Stealth and mimicry by deadly bacterial toxins.
Diphtheria toxin and exotoxin A are well-characterized members of the ADP-ribosyltransferase toxin family that function as virulence factors in the pathogenic bacteria Corynebacterium diphtheriae and Pseudomonas aeruginosa. Recent high-resolution structural data of the Michaelis (enzyme-substrate) complex of the P. aeruginosa toxin with an NAD(+) analog and eukaryotic elongation factor 2 (eEF2) have provided insights into the mechanism of inactivation of protein synthesis caused by these protein factors. In addition, rigorous steady-state and stopped-flow kinetic analyses of the toxin-catalyzed reaction, in combination with inhibitor studies, have resulted in a quantum leap in our understanding of the mechanistic details of this deadly enzyme mechanism. It is now apparent that these toxins use stealth and molecular mimicry in unleashing their toxic strategy in the infected host eukaryotic cell.
Yates
Susan P
SP
Department of Molecular and Cellular Biology, University of Guelph, Guelph, Ontario N1G 2W1, Canada.
Jørgensen
René
R
Andersen
Gregers R
GR
Merrill
A Rod
AR
D036002:ADP Ribose Transferases / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D000595:Amino Acid Sequence; D001427:Bacterial Toxins / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D001665:Binding Sites; D016384:Consensus Sequence; D004167:Diphtheria Toxin / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D005098:Exotoxins / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D006639:Histidine / Q000031:analogs & derivatives / Q000737:chemistry; D008958:Models, Molecular; D018716:Molecular Mimicry; D008969:Molecular Sequence Data; D016415:Sequence Alignment; D037521:Virulence Factors / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D000097668:Pseudomonas aeruginosa Exotoxin A
D036002:ADP Ribose Transferases; D001427:Bacterial Toxins; D004167:Diphtheria Toxin; D005098:Exotoxins; D006639:Histidine; D037521:Virulence Factors; D000097668:Pseudomonas aeruginosa Exotoxin A; C027527:diphthamide