1paq
From Proteopedia
(New page: 200px<br /><applet load="1paq" size="450" color="white" frame="true" align="right" spinBox="true" caption="1paq, resolution 2.30Å" /> '''CRYSTAL STRUCTURE OF...) |
|||
| Line 1: | Line 1: | ||
| - | [[Image:1paq.gif|left|200px]]<br /><applet load="1paq" size=" | + | [[Image:1paq.gif|left|200px]]<br /><applet load="1paq" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1paq, resolution 2.30Å" /> | caption="1paq, resolution 2.30Å" /> | ||
'''CRYSTAL STRUCTURE OF THE CATALYTIC FRAGMENT OF EUKARYOTIC INITIATION FACTOR 2B EPSILON'''<br /> | '''CRYSTAL STRUCTURE OF THE CATALYTIC FRAGMENT OF EUKARYOTIC INITIATION FACTOR 2B EPSILON'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Eukaryotic initiation factor (eIF) 2B catalyzes the nucleotide activation | + | Eukaryotic initiation factor (eIF) 2B catalyzes the nucleotide activation of eIF2 to its active GTP-bound state. The exchange activity has been mapped to the C terminus of the eIF2Bepsilon subunit. We have determined the crystal structure of residues 544-704 from yeast eIF2Bepsilon at 2.3-A resolution, and this fragment is an all-helical protein built around the conserved aromatic acidic (AA) boxes also found in eIF4G and eIF5. The eight helices are organized in a manner similar to HEAT repeats. The molecule is highly asymmetric with respect to surface charge and conservation. One area in the N terminus is proposed to be directly involved in catalysis. In agreement with this hypothesis, mutation of glutamate 569 is shown to be lethal. An acidic belt and a second area in the C terminus containing residues from the AA boxes are important for binding to eIF2. Two mutations causing the fatal human genetic disease leukoencephalopathy with vanishing white matter are buried and appear to disrupt the structural integrity of the catalytic domain rather than interfering directly with catalysis or binding of eIF2. |
==About this Structure== | ==About this Structure== | ||
| - | 1PAQ is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Saccharomyces_cerevisiae Saccharomyces cerevisiae]. Full crystallographic information is available from [http:// | + | 1PAQ is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Saccharomyces_cerevisiae Saccharomyces cerevisiae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1PAQ OCA]. |
==Reference== | ==Reference== | ||
| Line 13: | Line 13: | ||
[[Category: Saccharomyces cerevisiae]] | [[Category: Saccharomyces cerevisiae]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Andersen, G | + | [[Category: Andersen, G R.]] |
[[Category: Boesen, T.]] | [[Category: Boesen, T.]] | ||
| - | [[Category: Pavitt, G | + | [[Category: Pavitt, G D.]] |
[[Category: aa motif]] | [[Category: aa motif]] | ||
[[Category: heat repeat]] | [[Category: heat repeat]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:26:53 2008'' |
Revision as of 12:26, 21 February 2008
|
CRYSTAL STRUCTURE OF THE CATALYTIC FRAGMENT OF EUKARYOTIC INITIATION FACTOR 2B EPSILON
Overview
Eukaryotic initiation factor (eIF) 2B catalyzes the nucleotide activation of eIF2 to its active GTP-bound state. The exchange activity has been mapped to the C terminus of the eIF2Bepsilon subunit. We have determined the crystal structure of residues 544-704 from yeast eIF2Bepsilon at 2.3-A resolution, and this fragment is an all-helical protein built around the conserved aromatic acidic (AA) boxes also found in eIF4G and eIF5. The eight helices are organized in a manner similar to HEAT repeats. The molecule is highly asymmetric with respect to surface charge and conservation. One area in the N terminus is proposed to be directly involved in catalysis. In agreement with this hypothesis, mutation of glutamate 569 is shown to be lethal. An acidic belt and a second area in the C terminus containing residues from the AA boxes are important for binding to eIF2. Two mutations causing the fatal human genetic disease leukoencephalopathy with vanishing white matter are buried and appear to disrupt the structural integrity of the catalytic domain rather than interfering directly with catalysis or binding of eIF2.
About this Structure
1PAQ is a Single protein structure of sequence from Saccharomyces cerevisiae. Full crystallographic information is available from OCA.
Reference
Structure of the catalytic fragment of translation initiation factor 2B and identification of a critically important catalytic residue., Boesen T, Mohammad SS, Pavitt GD, Andersen GR, J Biol Chem. 2004 Mar 12;279(11):10584-92. Epub 2003 Dec 17. PMID:14681227
Page seeded by OCA on Thu Feb 21 14:26:53 2008
