Abstract
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.
| Originalsprog | Engelsk |
|---|---|
| Tidsskrift | Trends in Biochemical Sciences |
| Vol/bind | 31 |
| Udgave nummer | 2 |
| Sider (fra-til) | 123-133 |
| Antal sider | 11 |
| ISSN | 0968-0004 |
| DOI | |
| Status | Udgivet - feb. 2006 |
| Udgivet eksternt | Ja |
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.