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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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References listed in PDB file
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Key reference
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Title
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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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Authors
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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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Ref.
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J Med Chem, 2016,
59,
2244-2254.
[DOI no: ]
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PubMed id
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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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Secondary reference #1
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Title
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A tetrazolyl-Substituted subtype-Selective ampa receptor agonist.
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Authors
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S.B.Vogensen,
K.Frydenvang,
J.R.Greenwood,
G.Postorino,
B.Nielsen,
D.S.Pickering,
B.Ebert,
U.Bølcho,
J.Egebjerg,
M.Gajhede,
J.S.Kastrup,
T.N.Johansen,
R.P.Clausen,
P.Krogsgaard-Larsen.
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Ref.
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J Med Chem, 2007,
50,
2408-2414.
[DOI no: ]
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PubMed id
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