1y1m: Difference between revisions

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[[Image:1y1m.gif|left|200px]]<br /><applet load="1y1m" size="~~450~~" color="white" frame="true" align="right" spinBox="true"

[[Image:1y1m.gif|left|200px]]<br /><applet load="1y1m" size="350" color="white" frame="true" align="right" spinBox="true"

caption="1y1m, resolution 1.80Å" />

'''Crystal structure of the NR1 ligand binding core in complex with cycloleucine'''<br />

==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.

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 [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://~~ispc~~.weizmann.ac.il/oca-bin/ocashort?id=1Y1M OCA].

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==

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[[Category: protein-ligand complex; ligand-binding complex]]

''Page seeded by [http://~~ispc~~.weizmann.ac.il/oca OCA ] on ~~Wed Nov~~ 21 06:29:~~39 2007~~''

''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:00:54 2008''

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@@ Line 1: / Line 1: @@
-[[Image:1y1m.gif|left|200px]]<br /><applet load="1y1m" size="450" color="white" frame="true" align="right" spinBox="true"
+[[Image:1y1m.gif|left|200px]]<br /><applet load="1y1m" size="350" color="white" frame="true" align="right" spinBox="true"
 caption="1y1m, resolution 1.80&Aring;" />
 '''Crystal structure of the NR1 ligand binding core in complex with cycloleucine'''<br />
 ==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.
+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==
-Y1M 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://ispc.weizmann.ac.il/oca-bin/ocashort?id=1Y1M OCA].
+Y1M 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==
@@ Line 18: / Line 18: @@
 [[Category: protein-ligand complex; ligand-binding complex]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Wed Nov 21 06:29:39 2007''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:00:54 2008''