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2pbw

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{{STRUCTURE_2pbw| PDB=2pbw | SCENE= }}
{{STRUCTURE_2pbw| PDB=2pbw | SCENE= }}
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'''Crystal Structure of the Ligand-Binding Core of iGluR5 in Complex with the Partial agonist Domoic Acid at 2.5 A Resolution'''
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===Crystal Structure of the Ligand-Binding Core of iGluR5 in Complex with the Partial agonist Domoic Acid at 2.5 A Resolution===
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==Overview==
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More than 50 structures have been reported on the ligand-binding core of the ionotropic glutamate receptor iGluR2 that belongs to the 2-amino-3-(3-hydroxy-5-methyl-4-isoxazolyl)propionic acid-type of receptors. In contrast, the ligand-binding core of the kainic acid-type receptor iGluR5 has only been crystallized with three different ligands. Hence, additional structures of iGluR5 are needed to broaden the understanding of the ligand-binding properties of iGluR5, and the conformational changes leading to channel opening and closing. Here, we present two structures of the ligand-binding core of iGluR5; one as a complex with the partial agonist (2S,3S,4S)-3-carboxymethyl-4-[(1Z,3E,5R)-5-carboxy-1-methyl-hexa-1,3-dieny l]-pyrrolidine-2-carboxylic acid (domoic acid) and one as a complex with the antagonist (S)-2-amino-3-[5-tert-butyl-3-(phosphonomethoxy)-4-isoxazolyl]propionic acid ((S)-ATPO). In agreement with the partial agonist activity of domoic acid, the ligand-binding core of the iGluR5 complex is stabilized by domoic acid in a conformation that is 11 degrees more open than the conformation observed in the full agonist (S)-glutamic acid complex. This is primarily caused by the 5-carboxy-1-methyl-hexa-1,3-dienyl moiety of domoic acid and residues Val685-Thr690 of iGluR5. An even larger domain opening of 28 degrees is introduced upon binding of the antagonist (S)-ATPO. It appears that the span of domain opening is much larger in the ligand-binding core of iGluR5 (30 degrees) compared with what has been observed in iGluR2 (19 degrees ). Similarly, much larger variation in the distances between transmembrane linker residues in the two protomers comprising the dimer is observed in iGluR5 as compared with iGluR2.
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{{ABSTRACT_PUBMED_17581823}}
==About this Structure==
==About this Structure==
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[[Category: Agonist complex]]
[[Category: Agonist complex]]
[[Category: Membrane protein]]
[[Category: Membrane protein]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 12:48:33 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 20:04:09 2008''

Revision as of 17:04, 28 July 2008

Image:2pbw.png

Template:STRUCTURE 2pbw

Crystal Structure of the Ligand-Binding Core of iGluR5 in Complex with the Partial agonist Domoic Acid at 2.5 A Resolution

Template:ABSTRACT PUBMED 17581823

About this Structure

2PBW is a Single protein structure of sequence from Rattus norvegicus. Full crystallographic information is available from OCA.

Reference

Partial agonism and antagonism of the ionotropic glutamate receptor iGLuR5: structures of the ligand-binding core in complex with domoic acid and 2-amino-3-[5-tert-butyl-3-(phosphonomethoxy)-4-isoxazolyl]propionic acid., Hald H, Naur P, Pickering DS, Sprogoe D, Madsen U, Timmermann DB, Ahring PK, Liljefors T, Schousboe A, Egebjerg J, Gajhede M, Kastrup JS, J Biol Chem. 2007 Aug 31;282(35):25726-36. Epub 2007 Jun 20. PMID:17581823

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