1m5c: Difference between revisions
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[[Image:1m5c.gif|left|200px]] | [[Image:1m5c.gif|left|200px]] | ||
'''X-RAY STRUCTURE OF THE GLUR2 LIGAND BINDING CORE (S1S2J) IN COMPLEX WITH Br-HIBO AT 1.65 A RESOLUTION''' | {{Structure | ||
|PDB= 1m5c |SIZE=350|CAPTION= <scene name='initialview01'>1m5c</scene>, resolution 1.65Å | |||
|SITE= | |||
|LIGAND= <scene name='pdbligand=BRH:(S)-2-AMINO-3-(4-BROMO-3-HYDROXY-ISOXAZOL-5-YL)PROPIONIC ACID'>BRH</scene> | |||
|ACTIVITY= | |||
|GENE= GluR-2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10116 Rattus norvegicus]) | |||
}} | |||
'''X-RAY STRUCTURE OF THE GLUR2 LIGAND BINDING CORE (S1S2J) IN COMPLEX WITH Br-HIBO AT 1.65 A RESOLUTION''' | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
1M5C is a [ | 1M5C is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1M5C OCA]. | ||
==Reference== | ==Reference== | ||
Structural basis for AMPA receptor activation and ligand selectivity: crystal structures of five agonist complexes with the GluR2 ligand-binding core., Hogner A, Kastrup JS, Jin R, Liljefors T, Mayer ML, Egebjerg J, Larsen IK, Gouaux E, J Mol Biol. 2002 Sep 6;322(1):93-109. PMID:[http:// | Structural basis for AMPA receptor activation and ligand selectivity: crystal structures of five agonist complexes with the GluR2 ligand-binding core., Hogner A, Kastrup JS, Jin R, Liljefors T, Mayer ML, Egebjerg J, Larsen IK, Gouaux E, J Mol Biol. 2002 Sep 6;322(1):93-109. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/12215417 12215417] | ||
[[Category: Rattus norvegicus]] | [[Category: Rattus norvegicus]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
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[[Category: ligand binding core]] | [[Category: ligand binding core]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 12:39:05 2008'' | ||
Revision as of 13:39, 20 March 2008
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| , resolution 1.65Å | |||||||
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| Ligands: | |||||||
| Gene: | GluR-2 (Rattus norvegicus) | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
X-RAY STRUCTURE OF THE GLUR2 LIGAND BINDING CORE (S1S2J) IN COMPLEX WITH Br-HIBO AT 1.65 A RESOLUTION
OverviewOverview
Glutamate is the principal excitatory neurotransmitter within the mammalian CNS, playing an important role in many different functions in the brain such as learning and memory. In this study, a combination of molecular biology, X-ray structure determinations, as well as electrophysiology and binding experiments, has been used to increase our knowledge concerning the ionotropic glutamate receptor GluR2 at the molecular level. Five high-resolution X-ray structures of the ligand-binding domain of GluR2 (S1S2J) complexed with the three agonists (S)-2-amino-3-[3-hydroxy-5-(2-methyl-2H-tetrazol-5-yl)isoxazol-4-yl]propio nic acid (2-Me-Tet-AMPA), (S)-2-amino-3-(3-carboxy-5-methylisoxazol-4-yl)propionic acid (ACPA), and (S)-2-amino-3-(4-bromo-3-hydroxy-isoxazol-5-yl)propionic acid (Br-HIBO), as well as of a mutant thereof (S1S2J-Y702F) in complex with ACPA and Br-HIBO, have been determined. The structures reveal that AMPA agonists with an isoxazole moiety adopt different binding modes in the receptor, dependent on the substituents of the isoxazole. Br-HIBO displays selectivity among different AMPA receptor subunits, and the design and structure determination of the S1S2J-Y702F mutant in complex with Br-HIBO and ACPA have allowed us to explain the molecular mechanism behind this selectivity and to identify key residues for ligand recognition. The agonists induce the same degree of domain closure as AMPA, except for Br-HIBO, which shows a slightly lower degree of domain closure. An excellent correlation between domain closure and efficacy has been obtained from electrophysiology experiments undertaken on non-desensitising GluR2i(Q)-L483Y receptors expressed in oocytes, providing strong evidence that receptor activation occurs as a result of domain closure. The structural results, combined with the functional studies on the full-length receptor, form a powerful platform for the design of new selective agonists.
About this StructureAbout this Structure
1M5C is a Single protein structure of sequence from Rattus norvegicus. Full crystallographic information is available from OCA.
ReferenceReference
Structural basis for AMPA receptor activation and ligand selectivity: crystal structures of five agonist complexes with the GluR2 ligand-binding core., Hogner A, Kastrup JS, Jin R, Liljefors T, Mayer ML, Egebjerg J, Larsen IK, Gouaux E, J Mol Biol. 2002 Sep 6;322(1):93-109. PMID:12215417
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