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PDBsum entry 3lsl
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Transport protein
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PDB id
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3lsl
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Contents |
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* Residue conservation analysis
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PDB id:
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Transport protein
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Title:
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Piracetam bound to the ligand binding domain of glua2 (flop form)
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Structure:
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Glutamate receptor 2. Chain: a, d, g. Synonym: glur-2, glur-b, glur-k2, glutamate receptor ionotropic, ampa 2, ampa-selective glutamate receptor 2. Engineered: yes
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Source:
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Rattus norvegicus. Brown rat,rat,rats. Organism_taxid: 10116. Gene: gria2, glur2. Expressed in: escherichia coli. Expression_system_taxid: 562.
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Resolution:
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2.12Å
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R-factor:
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0.203
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R-free:
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0.263
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Authors:
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A.H.Ahmed,R.E.Oswald
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Key ref:
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A.H.Ahmed
and
R.E.Oswald
(2010).
Piracetam defines a new binding site for allosteric modulators of alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) receptors.
J Med Chem,
53,
2197-2203.
PubMed id:
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Date:
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12-Feb-10
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Release date:
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16-Mar-10
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PROCHECK
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Headers
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References
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P19491
(GRIA2_RAT) -
Glutamate receptor 2 from Rattus norvegicus
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Seq:
Struc:
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883 a.a.
258 a.a.*
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Key: |
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PfamA domain |
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Secondary structure |
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CATH domain |
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*
PDB and UniProt seqs differ
at 2 residue positions (black
crosses)
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J Med Chem
53:2197-2203
(2010)
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PubMed id:
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Piracetam defines a new binding site for allosteric modulators of alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) receptors.
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A.H.Ahmed,
R.E.Oswald.
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ABSTRACT
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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.
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Literature references that cite this PDB file's key reference
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PubMed id
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Reference
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J.Pøhlsgaard,
K.Frydenvang,
U.Madsen,
and
J.S.Kastrup
(2011).
Lessons from more than 80 structures of the GluA2 ligand-binding domain in complex with agonists, antagonists and allosteric modulators.
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Neuropharmacology,
60,
135-150.
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M.L.Mayer
(2011).
Structure and mechanism of glutamate receptor ion channel assembly, activation and modulation.
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Curr Opin Neurobiol,
21,
283-290.
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The most recent references are shown first.
Citation data come partly from CiteXplore and partly
from an automated harvesting procedure. Note that this is likely to be
only a partial list as not all journals are covered by
either method. However, we are continually building up the citation data
so more and more references will be included with time.
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Links
