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PDBsum entry 4gxs
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Membrane protein
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PDB id
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4gxs
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PDB id:
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| Name: |
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Membrane protein
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Title:
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Ligand binding domain of glua2 (ampa/glutamate receptor) bound to (-)- kaitocephalin
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Structure:
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Glutamate receptor 2. Chain: b, d. Fragment: unp residues 652-794. Synonym: glur-2, ampa-selective glutamate receptor 2, glur-b, glur- k2, glutamate receptor ionotropic, ampa 2, glua2. Engineered: yes
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Source:
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Rattus norvegicus. Brown rat,rat,rats. Organism_taxid: 10116. Gene: glur2, gria2, gria2. Glua2. Expressed in: escherichia coli. Expression_system_taxid: 469008.
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Resolution:
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1.96Å
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R-factor:
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0.189
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R-free:
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0.225
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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
et al.
(2012).
The structure of (-)-kaitocephalin bound to the ligand binding domain of the (S)-α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)/glutamate receptor, GluA2.
J Biol Chem,
287,
41007-41013.
PubMed id:
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Date:
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04-Sep-12
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Release date:
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17-Oct-12
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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 Biol Chem
287:41007-41013
(2012)
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PubMed id:
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The structure of (-)-kaitocephalin bound to the ligand binding domain of the (S)-α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)/glutamate receptor, GluA2.
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A.H.Ahmed,
M.Hamada,
T.Shinada,
Y.Ohfune,
L.Weerasinghe,
P.P.Garner,
R.E.Oswald.
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ABSTRACT
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Glutamate receptors mediate the majority of excitatory synaptic transmission in
the central nervous system, and excessive stimulation of these receptors is
involved in a variety of neurological disorders and neuronal damage from stroke.
The development of new subtype-specific antagonists would be of considerable
therapeutic interest. Natural products can provide important new lead compounds
for drug discovery. The only natural product known to inhibit glutamate
receptors competitively is (-)-kaitocephalin, which was isolated from the fungus
Eupenicillium shearii and found to protect CNS neurons from excitotoxicity.
Previous work has shown that it is a potent antagonist of some subtypes of
glutamate receptors (AMPA and NMDA, but not kainate). The structure of
kaitocephalin bound to the ligand binding domain of the AMPA receptor subtype,
GluA2, is reported here. The structure suggests how kaitocephalin can be used as
a scaffold to develop more selective and high affinity antagonists for glutamate
receptors.
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