1wvj
From Proteopedia
(New page: 200px<br /><applet load="1wvj" size="450" color="white" frame="true" align="right" spinBox="true" caption="1wvj, resolution 1.75Å" /> '''Exploring the GluR2 ...) |
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| - | [[Image:1wvj.gif|left|200px]]<br /><applet load="1wvj" size=" | + | [[Image:1wvj.gif|left|200px]]<br /><applet load="1wvj" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1wvj, resolution 1.75Å" /> | caption="1wvj, resolution 1.75Å" /> | ||
'''Exploring the GluR2 ligand-binding core in complex with the bicyclic AMPA analogue (S)-4-AHCP'''<br /> | '''Exploring the GluR2 ligand-binding core in complex with the bicyclic AMPA analogue (S)-4-AHCP'''<br /> | ||
==Overview== | ==Overview== | ||
| - | The X-ray structure of the ionotropic GluR2 ligand-binding core | + | The X-ray structure of the ionotropic GluR2 ligand-binding core (GluR2-S1S2J) in complex with the bicyclical AMPA analogue (S)-2-amino-3-(3-hydroxy-7,8-dihydro-6H-cyclohepta[d]-4-isoxazolyl)propion ic acid [(S)-4-AHCP] has been determined, as well as the binding pharmacology of this construct and of the full-length GluR2 receptor. (S)-4-AHCP binds with a glutamate-like binding mode and the ligand adopts two different conformations. The K(i) of (S)-4-AHCP at GluR2-S1S2J was determined to be 185 +/- 29 nM and at full-length GluR2(R)o it was 175 +/- 8 nM. (S)-4-AHCP appears to elicit partial agonism at GluR2 by inducing an intermediate degree of domain closure (17 degrees). Also, functionally (S)-4-AHCP has an efficacy of 0.38 at GluR2(Q)i, relative to (S)-glutamate. The proximity of bound (S)-4-AHCP to domain D2 prevents full D1-D2 domain closure, which is limited by steric repulsion, especially between Leu704 and the ligand. |
==About this Structure== | ==About this Structure== | ||
| - | 1WVJ is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus] with SO4, IBC and GOL as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http:// | + | 1WVJ is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus] with <scene name='pdbligand=SO4:'>SO4</scene>, <scene name='pdbligand=IBC:'>IBC</scene> and <scene name='pdbligand=GOL:'>GOL</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1WVJ OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Brehm, L.]] | [[Category: Brehm, L.]] | ||
[[Category: Gajhede, M.]] | [[Category: Gajhede, M.]] | ||
| - | [[Category: Greenwood, J | + | [[Category: Greenwood, J R.]] |
| - | [[Category: Kastrup, J | + | [[Category: Kastrup, J S.]] |
| - | [[Category: Nielsen, B | + | [[Category: Nielsen, B B.]] |
| - | [[Category: Pickering, D | + | [[Category: Pickering, D S.]] |
[[Category: Schousboe, A.]] | [[Category: Schousboe, A.]] | ||
[[Category: GOL]] | [[Category: GOL]] | ||
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[[Category: ligand-binding core]] | [[Category: ligand-binding core]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:48:32 2008'' |
Revision as of 13:48, 21 February 2008
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Exploring the GluR2 ligand-binding core in complex with the bicyclic AMPA analogue (S)-4-AHCP
Overview
The X-ray structure of the ionotropic GluR2 ligand-binding core (GluR2-S1S2J) in complex with the bicyclical AMPA analogue (S)-2-amino-3-(3-hydroxy-7,8-dihydro-6H-cyclohepta[d]-4-isoxazolyl)propion ic acid [(S)-4-AHCP] has been determined, as well as the binding pharmacology of this construct and of the full-length GluR2 receptor. (S)-4-AHCP binds with a glutamate-like binding mode and the ligand adopts two different conformations. The K(i) of (S)-4-AHCP at GluR2-S1S2J was determined to be 185 +/- 29 nM and at full-length GluR2(R)o it was 175 +/- 8 nM. (S)-4-AHCP appears to elicit partial agonism at GluR2 by inducing an intermediate degree of domain closure (17 degrees). Also, functionally (S)-4-AHCP has an efficacy of 0.38 at GluR2(Q)i, relative to (S)-glutamate. The proximity of bound (S)-4-AHCP to domain D2 prevents full D1-D2 domain closure, which is limited by steric repulsion, especially between Leu704 and the ligand.
About this Structure
1WVJ is a Single protein structure of sequence from Rattus norvegicus with , and as ligands. Full crystallographic information is available from OCA.
Reference
Exploring the GluR2 ligand-binding core in complex with the bicyclical AMPA analogue (S)-4-AHCP., Nielsen BB, Pickering DS, Greenwood JR, Brehm L, Gajhede M, Schousboe A, Kastrup JS, FEBS J. 2005 Apr;272(7):1639-48. PMID:15794751
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