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PDBsum entry 5fhn
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Membrane protein
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PDB id
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5fhn
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PDB id:
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Membrane protein
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Title:
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Crystal structure of the glua2 ligand-binding domain (s1s2j) in complex with (s)-2-amino-3-(5-(2-(3-methylbenzyl)-2h-tetrazol-5-yl)- 3-hydroxyisoxazol-4-yl)propanoic acid at 1.6 a resolution
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Structure:
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Glutamate receptor 2,glutamate receptor 2. Chain: a. Synonym: glur-2,ampa-selective glutamate receptor 2,glur-b,glur-k2, glutamate receptor ionotropic,ampa 2,glua2 ionotropic glutamate receptor a2,,glur-2,ampa-selective glutamate receptor 2,glur-b,glur- k2,glutamate receptor ionotropic,ampa 2,glua2ionotropic glutamate receptor a2. Engineered: yes. Other_details: ligand-binding domain of glua2. Transmembrane regions
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Source:
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Rattus norvegicus. Norway rat. Organism_taxid: 10116. Gene: gria2, glur2. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008. Expression_system_variant: origami b.
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Resolution:
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1.60Å
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R-factor:
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0.157
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R-free:
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0.186
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Authors:
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K.Frydenvang,J.S.Kastrup
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Key ref:
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S.Y.Wang
et al.
(2016).
Tweaking Subtype Selectivity and Agonist Efficacy at (S)-2-Amino-3-(3-hydroxy-5-methyl-isoxazol-4-yl)propionic acid (AMPA) Receptors in a Small Series of BnTetAMPA Analogues.
J Med Chem,
59,
2244-2254.
PubMed id:
DOI:
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Date:
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22-Dec-15
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Release date:
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02-Mar-16
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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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DOI no:
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J Med Chem
59:2244-2254
(2016)
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PubMed id:
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Tweaking Subtype Selectivity and Agonist Efficacy at (S)-2-Amino-3-(3-hydroxy-5-methyl-isoxazol-4-yl)propionic acid (AMPA) Receptors in a Small Series of BnTetAMPA Analogues.
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S.Y.Wang,
Y.Larsen,
C.V.Navarrete,
A.A.Jensen,
B.Nielsen,
A.Al-Musaed,
K.Frydenvang,
J.S.Kastrup,
D.S.Pickering,
R.P.Clausen.
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ABSTRACT
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A series of analogues of the
(S)-2-Amino-3-(3-hydroxy-5-methyl-isoxazol-4-yl)propionic acid (AMPA) receptor
agonist BnTetAMPA (5b) were synthesized and characterized pharmacologically in
radioligand binding assays at native and cloned AMPA receptors and functionally
by two-electrode voltage clamp electrophysiology at the four homomeric AMPA
receptors expressed in Xenopus laevis oocytes. The analogues 6 and 7 exhibit
very different pharmacological profiles with binding affinity preference for the
subtypes GluA1 and GluA3, respectively. X-ray crystal structures of three
ligands (6, 7, and 8) in complex with the agonist binding domain (ABD) of GluA2
show that they induce full domain closure despite their low agonist efficacies.
Trp767 in GluA2 ABD could be an important determinant for partial agonism of
this compound series at AMPA receptors, since agonist efficacy also correlated
with the location of the Trp767 side chain.
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