Stealth and mimicry by deadly bacterial toxins

Susan P. Yates, René Jørgensen, Gregers R. Andersen, A. Rod Merrill*

*Corresponding author

Publikation: Bidrag til tidsskriftReviewpeer review


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.

TidsskriftTrends in Biochemical Sciences
Udgave nummer2
Sider (fra-til)123-133
Antal sider11
StatusUdgivet - feb. 2006
Udgivet eksterntJa

Bibliografisk note

Funding Information:
We apologize to colleagues whose original work could not be cited owing to space limitations. We are grateful to Susannah Ellens for the bioinformatics analyses performed on the putative ART enzymes shown in Box 1 Figure I . This work was supported by Canadian Institutes of Health Research and Canadian Cystic Fibrosis Foundation (CCFF) grants (A.R.M.) and Human Frontier Science Program, European Union and SNF (Danish Research Council) (G.R.A.). S.P.Y. was a recipient of a CCFF predoctoral fellowship and R.J. was supported by a postdoctoral fellowship from the Villum Kann Rasmussen Foundation.

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