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PDBsum entry 3m3k
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Transport protein
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PDB id
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3m3k
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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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Ligand binding domain (s1s2) of glua3 (flop)
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Structure:
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Glutamate receptor 3. Chain: a, c, e. Fragment: unp residues 417-530, 658-799. Synonym: glur-3, glur-c, glur-k3, glutamate receptor ionotropic, ampa 3, ampa-selective glutamate receptor 3. Engineered: yes
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Source:
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Rattus norvegicus. Brown rat,rat,rats. Organism_taxid: 10116. Gene: gria3, glur3. Expressed in: escherichia coli. Expression_system_taxid: 469008.
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Resolution:
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1.79Å
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R-factor:
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0.202
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R-free:
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0.240
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Authors:
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A.H.Ahmed,C.P.Ptak,R.E.Oswald
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Key ref:
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A.H.Ahmed
et al.
(2010).
Molecular mechanism of flop selectivity and subsite recognition for an AMPA receptor allosteric modulator: structures of GluA2 and GluA3 in complexes with PEPA.
Biochemistry,
49,
2843-2850.
PubMed id:
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Date:
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09-Mar-10
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Release date:
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23-Mar-10
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PROCHECK
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Headers
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References
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P19492
(GRIA3_RAT) -
Glutamate receptor 3 from Rattus norvegicus
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Seq:
Struc:
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888 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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Biochemistry
49:2843-2850
(2010)
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PubMed id:
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Molecular mechanism of flop selectivity and subsite recognition for an AMPA receptor allosteric modulator: structures of GluA2 and GluA3 in complexes with PEPA.
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A.H.Ahmed,
C.P.Ptak,
R.E.Oswald.
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ABSTRACT
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Glutamate receptors are important potential drug targets for cognitive
enhancement and the treatment of schizophrenia in part because they are the most
prevalent excitatory neurotransmitter receptors in the vertebrate central
nervous system. One approach to the application of therapeutic agents to the
AMPA subtype of glutamate receptors is the use of allosteric modulators, which
promote dimerization by binding to a dimer interface thereby reducing the degree
of desensitization and deactivation. AMPA receptors exist in two alternatively
spliced variants (flip and flop) that differ in desensitization and receptor
activation profiles. Most of the structural information about modulators of the
AMPA receptor targets the flip subtype. We report here the crystal structure of
the flop-selective allosteric modulator, PEPA, bound to the binding domains of
the GluA2 and GluA3 flop isoforms of AMPA receptors. Specific hydrogen bonding
patterns can explain the preference for the flop isoform. This includes a
bidentate hydrogen bonding pattern between PEPA and N754 of the flop isoforms of
GluA2 and GluA3 (the corresponding position in the flip isoform is S754).
Comparison with other allosteric modulators provides a framework for the
development of new allosteric modulators with preferences for either the flip or
flop isoforms. In addition to interactions with N/S754, specific interactions of
the sulfonamide with conserved residues in the binding site are characteristics
of a number of allosteric modulators. These, in combination with variable
interactions with five subsites on the binding surface, lead to different
stoichiometries, orientations within the binding pockets, and functional
outcomes.
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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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S.S.Cha,
Y.J.An,
C.S.Jeong,
M.K.Kim,
S.G.Lee,
K.H.Lee,
and
B.H.Oh
(2012).
Experimental phasing using zinc anomalous scattering.
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Acta Crystallogr D Biol Crystallogr,
68,
1253-1258.
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PDB codes:
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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).
Glutamate receptor ion channels: where do all the calories go?
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Nat Struct Mol Biol,
18,
253-254.
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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.
Where a reference describes a PDB structure, the PDB
codes are
shown on the right.
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Links
