1ZM9

Structure of eEF2-ETA in complex with PJ34

Summary for 1ZM9

• Entry DOI: 10.2210/pdb1zm9/pdb
• Related: 1N0U 1XK9 1ZM2 1ZM3 1ZM4
• Descriptor: Elongation factor 2, exotoxin A, N~2~,N~2~-DIMETHYL-N~1~-(6-OXO-5,6-DIHYDROPHENANTHRIDIN-2-YL)GLYCINAMIDE (3 entities in total)
• Functional Keywords: elongation factor, toxin, adp-ribosylation, biosynthetic protein-transferase complex, biosynthetic protein/transferase
• Biological source: Pseudomonas aeruginosa; More
• Cellular location: Cytoplasm: P32324
• Total number of polymer chains: 6
• Total formula weight: 349022.00

Authors

Joergensen, R.,Merrill, A.R.,Yates, S.P.,Marquez, V.E.,Schwan, A.L.,Boesen, T.,Andersen, G.R. (deposition date: 2005-05-10, release date: 2005-05-24, Last modification date: 2023-08-23)

Primary citation

Joergensen, R.,Merrill, A.R.,Yates, S.P.,Marquez, V.E.,Schwan, A.L.,Boesen, T.,Andersen, G.R.
Exotoxin A-eEF2 complex structure indicates ADP ribosylation by ribosome mimicry.
Nature, 436:979-984, 2005

PubMed Abstract: 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.

PubMed: 16107839
DOI: 10.1038/nature03871

Experimental method

X-RAY DIFFRACTION (2.8 Å)