1zm3
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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. Active as NAD(+)--diphthamide ADP-ribosyltransferase, with EC number 2.4.2.36 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
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