1zm3: Difference between revisions
New page: left|200px<br /><applet load="1zm3" size="450" color="white" frame="true" align="right" spinBox="true" caption="1zm3, resolution 3.07Å" /> '''Structure of the apo... |
No edit summary |
||
| Line 1: | Line 1: | ||
[[Image:1zm3.gif|left|200px]]<br /><applet load="1zm3" size=" | [[Image:1zm3.gif|left|200px]]<br /><applet load="1zm3" size="350" color="white" frame="true" align="right" spinBox="true" | ||
caption="1zm3, resolution 3.07Å" /> | caption="1zm3, resolution 3.07Å" /> | ||
'''Structure of the apo eEF2-ETA complex'''<br /> | '''Structure of the apo eEF2-ETA complex'''<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== | ||
1ZM3 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]. Active as [http://en.wikipedia.org/wiki/NAD(+)--diphthamide_ADP-ribosyltransferase NAD(+)--diphthamide ADP-ribosyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.4.2.36 2.4.2.36] Full crystallographic information is available from [http:// | 1ZM3 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]. Active as [http://en.wikipedia.org/wiki/NAD(+)--diphthamide_ADP-ribosyltransferase NAD(+)--diphthamide ADP-ribosyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.4.2.36 2.4.2.36] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1ZM3 OCA]. | ||
==Reference== | ==Reference== | ||
| Line 15: | Line 15: | ||
[[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: adp-ribosylation]] | [[Category: adp-ribosylation]] | ||
[[Category: elongation factor]] | [[Category: elongation factor]] | ||
[[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 17:16, 21 February 2008
|
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
Page seeded by OCA on Thu Feb 21 16:16:53 2008