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Catalytic Site Atlas Version 2.2.12
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CSA entry for 1zm2
Original Entry
Title:
Biosynthetic protein/transferase
Compound:
Elongation factor 2
Mutant:
No
UniProt/Swiss-Prot:
P32324-EF2_YEAST
EC Class:
2.4.2.-
Other CSA Entries:
Overview of all sites for 1zm2
Homologues of 1zm2
Entries for UniProt/Swiss-Prot: P32324
Entries for EC: 2.4.2.-
Other Databases:
PDB entry: 1zm2
PDBsum entry: 1zm2
UniProt/Swiss-Prot: P32324
IntEnz entry: 2.4.2.-
Literature Report:
Introduction:
Exotoxin A (ETA) from Pseudomonas aeruginosa is an NAD+-diphthamide
ADP-ribosyltransferase from the enzyme family of mono-ADP-ribosyltransferases.
It catalyses the ADP-ribosylation of eukaryotic elongation factor 2 (eEF2).
Inactivation of eEF2 then results in cessation of protein synthesis and eventual cellular death.
Mechanism:
1. The reaction takes place via an SN1 mechanism.
2. Cleavage of the NC1-NN1 glycosidic bond in NAD+ takes place.
3. Glu 553 stabilises the positive charge on the oxacarbenium intermediate.
4. NE2 atom of the diphthamide residue of eEF2 nucleophilically attacks the NC1 atom on the oxacarbenium ion.
5. The product is then deprotonated and released.
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Found by:
Literature reference 

ResidueChainNumberUniProt numberFunctional part FunctionTargetDescription
GLUB 553 0Sidechain
ElectrostaticSubstrate
Glu 553 stabilises the oxacarbenium intermediate by hydrogen bonding with the 2'OH of the N ribose, after dissociation of nicotinamide.
Evidence from paper Evidence concerns Evidence type
PubMed ID 16107839 Current protein Residue is positioned appropriately (ligand position known)
PubMed ID 14733615 Current protein Residue is positioned appropriately (ligand position known)
PubMed ID 14733615 Current protein Mutagenesis of residue
Notes:
There must also be a residue present to protonate the leaving nicotinamide, and deprotonate the product, however this isn't mentioned in any papers. Tyr 481 may also be catalytic, having the same role as Glu 553, in stabilising the intermediate, but no evidence of this has been found.
References:
1
Elucidation of eukaryotic elongation factor-2 contact sites within the catalytic domain of Pseudomonas aeruginosa exotoxin A.
S. P. Yates and A. R. Merrill
Biochem J 379, (Pt 3) 563-72, (2004).
14733615
2
Exotoxin A-eEF2 complex structure indicates ADP ribosylation by ribosome mimicry.
R. Jørgensen and A. R. Merrill and S. P. Yates and V. E. Marquez and A. L. Schwan and T. Boesen and G. R. Andersen
Nature 436, (7053) 979-84, (2005).
16107839
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