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PDBsum entry 4igr
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Membrane protein
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PDB id
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4igr
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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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Crystal structure of the kainate receptor gluk3 ligand-binding domain in complex with the agonist za302
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Structure:
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Glutamate receptor, ionotropic kainate 3. Chain: a. Fragment: ligand-binding domain, unp residues 432-546, 669-806. Synonym: glutamate receptor 7, glur-7, glur7. Engineered: yes
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Source:
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Rattus norvegicus. Rat. Organism_taxid: 10116. Gene: glur7, grik3. Expressed in: escherichia coli. Expression_system_taxid: 562.
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Resolution:
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2.65Å
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R-factor:
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0.201
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R-free:
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0.267
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Authors:
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A.P.Larsen,R.Venskutonyte,M.Gajhede,J.S.Kastrup,K.Frydenvang
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Key ref:
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Z.Assaf
et al.
(2013).
Chemoenzymatic synthesis of new 2,4-syn-functionalized (S)-glutamate analogues and structure-activity relationship studies at ionotropic glutamate receptors and excitatory amino acid transporters.
J Med Chem,
56,
1614-1628.
PubMed id:
DOI:
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Date:
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18-Dec-12
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Release date:
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06-Mar-13
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PROCHECK
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Headers
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References
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P42264
(GRIK3_RAT) -
Glutamate receptor ionotropic, kainate 3 from Rattus norvegicus
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Seq:
Struc:
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919 a.a.
253 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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DOI no:
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J Med Chem
56:1614-1628
(2013)
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PubMed id:
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Chemoenzymatic synthesis of new 2,4-syn-functionalized (S)-glutamate analogues and structure-activity relationship studies at ionotropic glutamate receptors and excitatory amino acid transporters.
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Z.Assaf,
A.P.Larsen,
R.Venskutonytė,
L.Han,
B.Abrahamsen,
B.Nielsen,
M.Gajhede,
J.S.Kastrup,
A.A.Jensen,
D.S.Pickering,
K.Frydenvang,
T.Gefflaut,
L.Bunch.
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ABSTRACT
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In the mammalian central nervous system, (S)-glutamate (Glu) is released from
the presynaptic neuron where it activates a plethora of pre- and postsynaptic
Glu receptors. The fast acting ionotropic Glu receptors (iGluRs) are ligand
gated ion channels and are believed to be involved in a vast number of
neurological functions such as memory and learning, synaptic plasticity, and
motor function. The synthesis of 14 enantiopure 2,4-syn-Glu analogues 2b-p is
accessed by a short and efficient chemoenzymatic approach starting from readily
available cyclohexanone 3. Pharmacological characterization at the iGluRs and
EAAT1-3 subtypes revealed analogue 2i as a selective GluK1 ligand with low
nanomolar affinity. Two X-ray crystal structures of the key analogue 2i in the
ligand-binding domain (LBD) of GluA2 and GluK3 were determined. Partial domain
closure was seen in the GluA2-LBD complex with 2i comparable to that induced by
kainate. In contrast, full domain closure was observed in the GluK3-LBD complex
with 2i, similar to that of GluK3-LBD with glutamate bound.
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