1zm3
| |||||||
| , resolution 3.07Å | |||||||
|---|---|---|---|---|---|---|---|
| Activity: | NAD(+)--diphthamide ADP-ribosyltransferase, with EC number 2.4.2.36 | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Structure of the apo eEF2-ETA complex
OverviewOverview
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.
About this StructureAbout this Structure
1ZM3 is a Protein complex structure of sequences from Pseudomonas aeruginosa and Saccharomyces cerevisiae. Full crystallographic information is available from OCA.
ReferenceReference
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
Page seeded by OCA on Thu Mar 20 15:37:11 2008