3LSF: Piracetam Bound To The Ligand Binding Domain Of Glua2

Citation:
Abstract
Glutamate receptors are the most prevalent excitatory neurotransmitter receptors in the vertebrate central nervous system and are important potential drug targets for cognitive enhancement and the treatment of schizophrenia. Allosteric modulators of AMPA receptors promote dimerization by binding to a dimer interface and reducing desensitization and deactivation. The pyrrolidine allosteric modulators, piracetam and aniracetam, were among the first of this class of drugs to be discovered. We have determined the structure of the ligand binding domain of the AMPA receptor subtypes GluA2 and GluA3 with piracetam and a corresponding structure of GluA3 with aniracetam. Both drugs bind to GluA2 and GluA3 in a very similar manner, suggesting little subunit specificity. However, the binding sites for piracetam and aniracetam differ considerably. Aniracetam binds to a symmetrical site at the center of the dimer interface. Piracetam binds to multiple sites along the dimer interface with low occupation, one of which is a unique binding site for potential allosteric modulators. This new site may be of importance in the design of new allosteric regulators.
PDB ID: 3LSFDownload
MMDB ID: 80863
PDB Deposition Date: 2010/2/12
Updated in MMDB: 2017/08
Experimental Method:
x-ray diffraction
Resolution: 1.85  Å
Source Organism:
Similar Structures:
Biological Unit for 3LSF: dimeric; determined by author and by software (PISA)
Molecular Components in 3LSF
Label Count Molecule
Proteins (2 molecules)
2
Glutamate Receptor 2(Gene symbol: Gria2)
Molecule annotation
Chemicals (13 molecules)
1
3
2
6
3
4
* Click molecule labels to explore molecular sequence information.

Citing MMDB
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