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PDBsum entry 4nwd
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Membrane protein/agonist
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PDB id
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4nwd
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PDB id:
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Membrane protein/agonist
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Title:
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Crystal structure of the kainate receptor gluk3 ligand-binding domain in complex with the agonist (2s,4r)-4-(3-methylamino-3-oxopropyl) glutamic acid at 2.6 a resolution
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Structure:
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Glutamate receptor ionotropic, kainate 3. Chain: a. Fragment: unp residues 432-546 and unp residues 669-806. Synonym: gluk3, glutamate receptor 7, glur-7, glur7. Engineered: yes
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Source:
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Rattus norvegicus. Brown rat,rat,rats. Organism_taxid: 10116. Gene: glur7, grik3. Expressed in: escherichia coli. Expression_system_taxid: 562.
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Resolution:
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2.60Å
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R-factor:
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0.208
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R-free:
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0.265
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Authors:
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R.Venskutonyte,A.P.Larsen,K.Frydenvang,M.Gajhede,J.S.Kastrup
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Key ref:
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R.Venskutonytė
et al.
(2014).
Molecular recognition of two 2,4-syn-functionalized (S)-glutamate analogues by the kainate receptor GluK3 ligand binding domain.
Chemmedchem,
9,
2254-2259.
PubMed id:
DOI:
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Date:
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06-Dec-13
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Release date:
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06-Aug-14
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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.
254 a.a.
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Key: |
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Secondary structure |
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CATH domain |
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DOI no:
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Chemmedchem
9:2254-2259
(2014)
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PubMed id:
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Molecular recognition of two 2,4-syn-functionalized (S)-glutamate analogues by the kainate receptor GluK3 ligand binding domain.
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R.Venskutonytė,
A.P.Larsen,
K.Frydenvang,
M.Gajhede,
E.Sagot,
Z.Assaf,
T.Gefflaut,
D.S.Pickering,
L.Bunch,
J.S.Kastrup.
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ABSTRACT
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The kainate receptors are the least studied subfamily of ionotropic glutamate
receptors. These receptors are thought to have a neuromodulatory role and have
been associated with a variety of disorders in the central nervous system. This
makes kainate receptors interesting potential drug targets. Today, structures of
the ligand binding domain (LBD) of the kainate receptor GluK3 are only known in
complex with the endogenous agonist glutamate, the natural product kainate, and
two synthetic agonists. Herein we report structures of GluK3 LBD in complex with
two 2,4-syn-functionalized (S)-glutamate analogues to investigate their
structural potential as chemical scaffolds. Similar binding affinities at GluK3
were determined for the 2-(methylcarbamoyl)ethyl analogue (Ki =4.0 μM) and
the 2-(methoxycarbonyl)ethyl analogue (Ki =1.7 μM), in agreement with the
similar positioning of the compounds within the binding pocket. As the binding
affinity is similar to that of glutamate, this type of Cγ substituent could be
used as a scaffold for introduction of even larger substituents reaching into
unexplored binding site regions to achieve subtype selectivity.
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