1y1m
From Proteopedia
(New page: 200px<br /><applet load="1y1m" size="450" color="white" frame="true" align="right" spinBox="true" caption="1y1m, resolution 1.80Å" /> '''Crystal structure of...) |
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| - | [[Image:1y1m.gif|left|200px]]<br /><applet load="1y1m" size=" | + | [[Image:1y1m.gif|left|200px]]<br /><applet load="1y1m" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1y1m, resolution 1.80Å" /> | caption="1y1m, resolution 1.80Å" /> | ||
'''Crystal structure of the NR1 ligand binding core in complex with cycloleucine'''<br /> | '''Crystal structure of the NR1 ligand binding core in complex with cycloleucine'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Partial agonists produce submaximal activation of ligand-gated ion | + | Partial agonists produce submaximal activation of ligand-gated ion channels. To address the question of partial agonist action at the NR1 subunit of the NMDA receptor, we performed crystallographic and electrophysiological studies with 1-aminocyclopropane-1-carboxylic acid (ACPC), 1-aminocyclobutane-1-carboxylic acid (ACBC), and 1-aminocyclopentane-1-carboxylic acid (cycloleucine), three compounds with incrementally larger carbocyclic rings. Whereas ACPC and ACBC partially activate the NMDA receptor by 80% and 42%, respectively, their cocrystal structures of the NR1 ligand binding core show the same degree of domain closure as found in the complex with glycine, a full agonist, illustrating that the NR1 subunit provides a new paradigm for partial agonist action that is distinct from that of the evolutionarily related GluR2, AMPA-sensitive receptor. Cycloleucine behaves as an antagonist and stabilizes an open-cleft conformation. The NR1-cycloleucine complex forms a dimer that is similar to the GluR2 dimer, thereby suggesting a conserved mode of subunit-subunit interaction in AMPA and NMDA receptors. |
==About this Structure== | ==About this Structure== | ||
| - | 1Y1M 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 AC5 as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http:// | + | 1Y1M 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=AC5:'>AC5</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1Y1M OCA]. |
==Reference== | ==Reference== | ||
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[[Category: protein-ligand complex; ligand-binding complex]] | [[Category: protein-ligand complex; ligand-binding complex]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:00:54 2008'' |
Revision as of 14:00, 21 February 2008
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Crystal structure of the NR1 ligand binding core in complex with cycloleucine
Overview
Partial agonists produce submaximal activation of ligand-gated ion channels. To address the question of partial agonist action at the NR1 subunit of the NMDA receptor, we performed crystallographic and electrophysiological studies with 1-aminocyclopropane-1-carboxylic acid (ACPC), 1-aminocyclobutane-1-carboxylic acid (ACBC), and 1-aminocyclopentane-1-carboxylic acid (cycloleucine), three compounds with incrementally larger carbocyclic rings. Whereas ACPC and ACBC partially activate the NMDA receptor by 80% and 42%, respectively, their cocrystal structures of the NR1 ligand binding core show the same degree of domain closure as found in the complex with glycine, a full agonist, illustrating that the NR1 subunit provides a new paradigm for partial agonist action that is distinct from that of the evolutionarily related GluR2, AMPA-sensitive receptor. Cycloleucine behaves as an antagonist and stabilizes an open-cleft conformation. The NR1-cycloleucine complex forms a dimer that is similar to the GluR2 dimer, thereby suggesting a conserved mode of subunit-subunit interaction in AMPA and NMDA receptors.
About this Structure
1Y1M is a Single protein structure of sequence from Rattus norvegicus with as ligand. Full crystallographic information is available from OCA.
Reference
Mechanism of partial agonist action at the NR1 subunit of NMDA receptors., Inanobe A, Furukawa H, Gouaux E, Neuron. 2005 Jul 7;47(1):71-84. PMID:15996549
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