2e1r
From Proteopedia
(New page: 200px<br /><applet load="2e1r" size="450" color="white" frame="true" align="right" spinBox="true" caption="2e1r, resolution 3.15Å" /> '''Structure of eEF2 in...) |
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| - | [[Image:2e1r.gif|left|200px]]<br /><applet load="2e1r" size=" | + | [[Image:2e1r.gif|left|200px]]<br /><applet load="2e1r" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="2e1r, resolution 3.15Å" /> | caption="2e1r, resolution 3.15Å" /> | ||
'''Structure of eEF2 in complex with a sordarin derivative'''<br /> | '''Structure of eEF2 in complex with a sordarin derivative'''<br /> | ||
==Overview== | ==Overview== | ||
| - | The sordarins are fungal specific inhibitors of the translation factor | + | The sordarins are fungal specific inhibitors of the translation factor eEF2, which catalyzes the translocation of tRNA and mRNA after peptide bond formation. We have determined the crystal structures of eEF2 in complex with two novel sordarin derivatives. In both structures, the three domains of eEF2 that form the ligand-binding pocket are oriented in a different manner relative to the rest of eEF2 compared with our previous structure of eEF2 in complex with the parent natural product sordarin. Yeast eEF2 is also shown to bind adenylic nucleotides, which can be displaced by sordarin, suggesting that ADP or ATP also bind to the three C-terminal domains of eEF2. Fusidic acid is a universal inhibitor of translation that targets EF-G or eEF2 and is widely used as an antibiotic against Gram-positive bacteria. Based on mutations conferring resistance to fusidic acid, cryo-EM reconstructions, and x-ray structures of eEF2, EF-G, and an EF-G homolog, we suggest that the conformation of EF-G stalled on the 70 S ribosome by fusidic acid is similar to that of eEF2 trapped on the 80 S ribosome by sordarin. |
==About this Structure== | ==About this Structure== | ||
| - | 2E1R is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Saccharomyces_cerevisiae Saccharomyces cerevisiae] with SOD and GDP as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http:// | + | 2E1R is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Saccharomyces_cerevisiae Saccharomyces cerevisiae] with <scene name='pdbligand=SOD:'>SOD</scene> and <scene name='pdbligand=GDP:'>GDP</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2E1R OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Saccharomyces cerevisiae]] | [[Category: Saccharomyces cerevisiae]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Andersen, G | + | [[Category: Andersen, G R.]] |
| - | [[Category: Mosley, R | + | [[Category: Mosley, R T.]] |
[[Category: Soe, R.]] | [[Category: Soe, R.]] | ||
[[Category: GDP]] | [[Category: GDP]] | ||
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[[Category: protein-ligand complex]] | [[Category: protein-ligand complex]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 17:04:54 2008'' |
Revision as of 15:04, 21 February 2008
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Structure of eEF2 in complex with a sordarin derivative
Overview
The sordarins are fungal specific inhibitors of the translation factor eEF2, which catalyzes the translocation of tRNA and mRNA after peptide bond formation. We have determined the crystal structures of eEF2 in complex with two novel sordarin derivatives. In both structures, the three domains of eEF2 that form the ligand-binding pocket are oriented in a different manner relative to the rest of eEF2 compared with our previous structure of eEF2 in complex with the parent natural product sordarin. Yeast eEF2 is also shown to bind adenylic nucleotides, which can be displaced by sordarin, suggesting that ADP or ATP also bind to the three C-terminal domains of eEF2. Fusidic acid is a universal inhibitor of translation that targets EF-G or eEF2 and is widely used as an antibiotic against Gram-positive bacteria. Based on mutations conferring resistance to fusidic acid, cryo-EM reconstructions, and x-ray structures of eEF2, EF-G, and an EF-G homolog, we suggest that the conformation of EF-G stalled on the 70 S ribosome by fusidic acid is similar to that of eEF2 trapped on the 80 S ribosome by sordarin.
About this Structure
2E1R is a Single protein structure of sequence from Saccharomyces cerevisiae with and as ligands. Full crystallographic information is available from OCA.
Reference
Sordarin derivatives induce a novel conformation of the yeast ribosome translocation factor eEF2., Soe R, Mosley RT, Justice M, Nielsen-Kahn J, Shastry M, Merrill AR, Andersen GR, J Biol Chem. 2007 Jan 5;282(1):657-66. Epub 2006 Nov 2. PMID:17082187
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