1zm2
From Proteopedia
(New page: 200px<br /><applet load="1zm2" size="450" color="white" frame="true" align="right" spinBox="true" caption="1zm2, resolution 3.07Å" /> '''Structure of ADP-rib...) |
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| - | [[Image:1zm2.gif|left|200px]]<br /><applet load="1zm2" size=" | + | [[Image:1zm2.gif|left|200px]]<br /><applet load="1zm2" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1zm2, resolution 3.07Å" /> | caption="1zm2, resolution 3.07Å" /> | ||
'''Structure of ADP-ribosylated eEF2 in complex with catalytic fragment of ETA'''<br /> | '''Structure of ADP-ribosylated eEF2 in complex with catalytic fragment of ETA'''<br /> | ||
==Overview== | ==Overview== | ||
| - | The bacteria causing diphtheria, whooping cough, cholera and other | + | 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== | ==About this Structure== | ||
| - | 1ZM2 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Pseudomonas_aeruginosa Pseudomonas aeruginosa] and [http://en.wikipedia.org/wiki/Saccharomyces_cerevisiae Saccharomyces cerevisiae] with APR as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http:// | + | 1ZM2 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Pseudomonas_aeruginosa Pseudomonas aeruginosa] and [http://en.wikipedia.org/wiki/Saccharomyces_cerevisiae Saccharomyces cerevisiae] with <scene name='pdbligand=APR:'>APR</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1ZM2 OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Pseudomonas aeruginosa]] | [[Category: Pseudomonas aeruginosa]] | ||
[[Category: Saccharomyces cerevisiae]] | [[Category: Saccharomyces cerevisiae]] | ||
| - | [[Category: Andersen, G | + | [[Category: Andersen, G R.]] |
[[Category: Boesen, T.]] | [[Category: Boesen, T.]] | ||
[[Category: Joergensen, R.]] | [[Category: Joergensen, R.]] | ||
| - | [[Category: Marquez, V | + | [[Category: Marquez, V E.]] |
| - | [[Category: Merrill, A | + | [[Category: Merrill, A R.]] |
| - | [[Category: Schwan, A | + | [[Category: Schwan, A L.]] |
| - | [[Category: Yates, S | + | [[Category: Yates, S P.]] |
[[Category: APR]] | [[Category: APR]] | ||
[[Category: adp-ribosylation]] | [[Category: adp-ribosylation]] | ||
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[[Category: toxin]] | [[Category: toxin]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:16:53 2008'' |
Revision as of 14:16, 21 February 2008
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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 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
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