1zm2
From Proteopedia
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Structure of ADP-ribosylated eEF2 in complex with catalytic fragment of ETA
Overview
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 Structure
1ZM2 is a Protein complex structure of sequences from Pseudomonas aeruginosa and Saccharomyces cerevisiae with APR as ligand. Full crystallographic information is available from OCA.
Reference
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 Wed Nov 21 07:31:41 2007
