1Y1Z

Crystal structure of the NR1 ligand binding core in complex with ACBC

Summary for 1Y1Z

• Entry DOI: 10.2210/pdb1y1z/pdb
• Related: 1PB7 1PB8 1PB9 1PBQ 1Y1M 1Y20
• Descriptor: Glutamate [NMDA] receptor subunit zeta 1, 1-AMINOCYCLOBUTANECARBOXLIC ACID (3 entities in total)
• Functional Keywords: protein-ligand complex; ligand-binding complex, ligand binding protein
• Biological source: Rattus norvegicus (Norway rat); More
• Cellular location: Cell membrane ; Multi-pass membrane protein : P35439
• Total number of polymer chains: 1
• Total formula weight: 33455.16

Authors

Inanobe, A.,Gouaux, E. (deposition date: 2004-11-19, release date: 2005-07-12, Last modification date: 2024-10-30)

Primary citation

Inanobe, A.,Furukawa, H.,Gouaux, E.
Mechanism of Partial Agonist Action at the NR1 Subunit of NMDA Receptors.
Neuron, 47:71-84, 2005

PubMed Abstract: 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.

PubMed: 15996549
DOI: 10.1016/j.neuron.2005.05.022

Experimental method

X-RAY DIFFRACTION (1.5 Å)