Structural highlights
3b82 is a 6 chain structure with sequence from "bacillus_aeruginosus"_(schroeter_1872)_trevisan_1885 "bacillus aeruginosus" (schroeter 1872) trevisan 1885 and Saccharomyces cerevisiae. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
|
| Ligands: | |
| NonStd Res: | |
| Related: | 1zm2, 1zm3, 1zm4, 1zm9, 3b78, 3b8h |
| Gene: | eta ("Bacillus aeruginosus" (Schroeter 1872) Trevisan 1885) |
| Activity: | NAD(+)--diphthamide ADP-ribosyltransferase, with EC number 2.4.2.36 |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum |
Function
[TOXA_PSEAE] An NAD-dependent ADP-ribosyltransferase (ADPRT). Catalyzes the transfer of the ADP ribosyl moiety of oxidized NAD (NAD(+)) onto eukaryotic elongation factor 2 (eEF-2) thus arresting protein synthesis. Has an LD(50) of 65 ng/ml against the human lung epithelial cell line C38.[1]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Exotoxin A (ExoA) from Pseudomonas aeruginosa is an important virulence factor that belongs to a class of exotoxins that are secreted by pathogenic bacteria which cause human diseases such as cholera, diphtheria, pneumonia and whooping cough. We present the first crystal structures, to our knowledge, of ExoA in complex with elongation factor 2 (eEF2) and intact NAD(+), which indicate a direct role of two active-site loops in ExoA during the catalytic cycle. One loop moves to form a solvent cover for the active site of the enzyme and reaches towards the target residue (diphthamide) in eEF2 forming an important hydrogen bond. The NAD(+) substrate adopts a conformation remarkably different from that of the NAD(+) analogue, betaTAD, observed in previous structures, and fails to trigger any loop movements. Mutational studies of the two loops in the toxin identify several residues important for catalytic activity, in particular Glu 546 and Arg 551, clearly supporting the new complex structures. On the basis of these data, we propose a transition-state model for the toxin-catalysed reaction.
The nature and character of the transition state for the ADP-ribosyltransferase reaction.,Jorgensen R, Wang Y, Visschedyk D, Merrill AR EMBO Rep. 2008 Aug;9(8):802-9. Epub 2008 Jun 27. PMID:18583986[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Jorgensen R, Purdy AE, Fieldhouse RJ, Kimber MS, Bartlett DH, Rod Merrill A. Cholix toxin, a novel ADP-ribosylating factor from vibrio cholerae. J Biol Chem. 2008 Feb 25;. PMID:18276581 doi:M710008200
- ↑ Jorgensen R, Wang Y, Visschedyk D, Merrill AR. The nature and character of the transition state for the ADP-ribosyltransferase reaction. EMBO Rep. 2008 Aug;9(8):802-9. Epub 2008 Jun 27. PMID:18583986 doi:10.1038/embor.2008.90
