Structural highlights
1zm9 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.
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| Ligands: | |
| NonStd Res: | |
| Related: | 1n0u, 1xk9, 1zm2, 1zm3, 1zm4 |
| Activity: | NAD(+)--diphthamide ADP-ribosyltransferase, with EC number 2.4.2.36 |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
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
The bacteria causing diphtheria, whooping cough, cholera and other diseases secrete mono-ADP-ribosylating toxins that modify intracellular proteins. Here, we describe four structures of a catalytically active complex between a fragment of Pseudomonas aeruginosa exotoxin A (ETA) and its protein substrate, translation elongation factor 2 (eEF2). The target residue in eEF2, diphthamide (a modified histidine), spans across a cleft and faces the two phosphates and a ribose of the non-hydrolysable NAD+ analogue, betaTAD. This suggests that the diphthamide is involved in triggering NAD+ cleavage and interacting with the proposed oxacarbenium intermediate during the nucleophilic substitution reaction, explaining the requirement of diphthamide for ADP ribosylation. Diphtheria toxin may recognize eEF2 in a manner similar to ETA. Notably, the toxin-bound betaTAD phosphates mimic the phosphate backbone of two nucleotides in a conformational switch of 18S rRNA, thereby achieving universal recognition of eEF2 by ETA.
Exotoxin A-eEF2 complex structure indicates ADP ribosylation by ribosome mimicry.,Jorgensen R, Merrill AR, Yates SP, Marquez VE, Schwan AL, Boesen T, Andersen GR Nature. 2005 Aug 18;436(7053):979-84. PMID:16107839[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Jorgensen R, Merrill AR, Yates SP, Marquez VE, Schwan AL, Boesen T, Andersen GR. Exotoxin A-eEF2 complex structure indicates ADP ribosylation by ribosome mimicry. Nature. 2005 Aug 18;436(7053):979-84. PMID:16107839 doi:http://dx.doi.org/10.1038/nature03871
