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PDBsum entry 4jwy
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Transport protein
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PDB id
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4jwy
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PDB id:
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| Name: |
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Transport protein
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Title:
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Glun2d ligand-binding core in complex with propyl-nhp5g
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Structure:
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Glutamate receptor ionotropic, nmda 2d. Chain: a. Fragment: ligand binding domain. Synonym: glun2d, glutamate [nmda] receptor subunit epsilon-4, n- methyl d-aspartate receptor subtype 2d, nmdar2d, nr2d. Engineered: yes
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Source:
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Rattus norvegicus. Brown rat,rat,rats. Organism_taxid: 10116. Gene: grin2d, glun2d. Expressed in: escherichia coli. Expression_system_taxid: 469008.
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Resolution:
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2.00Å
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R-factor:
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0.193
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R-free:
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0.233
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Authors:
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K.B.Hansen,N.Tajima,R.Risgaard,R.E.Perszyk,L.Jorgensen,K.M.Vance, K.K.Ogden,R.P.Clausen,H.Furukawa,S.F.Traynelis
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Key ref:
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K.B.Hansen
et al.
(2013).
Structural determinants of agonist efficacy at the glutamate binding site of N-methyl-D-aspartate receptors.
Mol Pharmacol,
84,
114-127.
PubMed id:
DOI:
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Date:
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27-Mar-13
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Release date:
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29-May-13
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PROCHECK
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Headers
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References
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Q62645
(NMDE4_RAT) -
Glutamate receptor ionotropic, NMDA 2D from Rattus norvegicus
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Seq:
Struc:
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1323 a.a.
269 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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Mol Pharmacol
84:114-127
(2013)
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PubMed id:
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Structural determinants of agonist efficacy at the glutamate binding site of N-methyl-D-aspartate receptors.
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K.B.Hansen,
N.Tajima,
R.Risgaard,
R.E.Perszyk,
L.Jørgensen,
K.M.Vance,
K.K.Ogden,
R.P.Clausen,
H.Furukawa,
S.F.Traynelis.
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ABSTRACT
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N-methyl-d-aspartate (NMDA) receptors are ligand-gated ion channels assembled
from GluN1 and GluN2 subunits. We used a series of N-hydroxypyrazole-5-glycine
(NHP5G) partial agonists at the GluN2 glutamate binding site as tools to study
activation of GluN1/GluN2A and GluN1/GluN2D NMDA receptor subtypes. Using
two-electrode voltage-clamp electrophysiology, fast-application patch-clamp, and
single-channel recordings, we show that propyl- and ethyl-substituted NHP5G
agonists have a broad range of agonist efficacies relative to the full agonist
glutamate (<1-72%). Crystal structures of the agonist binding domains (ABDs)
of GluN2A and GluN2D do not reveal any differences in the overall domain
conformation induced by binding of the full agonist glutamate or the partial
agonist propyl-NHP5G, which is strikingly different from ABD structures of
2-amino-3-(3-hydroxy-5-methylisoxazol-4-yl)propanoate (AMPA) and kainate
receptors bound to full and partial agonists. Subsequent evaluation of relative
NHP5G agonist efficacy at GluN2A-GluN2D chimeric subunits implicates the
amino-terminal domain (ATD) as a strong determinant of agonist efficacy,
suggesting that interdomain interactions between the ABD and the ATD may be a
central element in controlling the manner by which agonist binding leads to
channel opening. We propose that variation in the overall receptor conformation,
which is strongly influenced by the nature of interdomain interactions in
resting and active states, mediates differences in agonist efficacy and partial
agonism at the GluN2 subunits.
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Links
