 |
PDBsum entry 4iy5
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Membrane protein
|
PDB id
|
|
|
|
4iy5
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
PDB id:
|
|
|
|
| Name: |
|
Membrane protein
|
|
|
Title:
|
|
Crystal structure of the glua2 ligand-binding domain (s1s2j-l483y- n754s) in complex with glutamate and cx516 at 2.0 a resolution
|
|
Structure:
|
|
Glutamate receptor 2. Chain: a, b. Fragment: ligand binding domain, unp residues 413-527, 653-796. Synonym: glur-2, ampa-selective glutamate receptor 2, glur-b, glur- k2, glutamate receptor ionotropic, ampa 2, glua2. Engineered: yes. Mutation: yes
|
|
Source:
|
|
Rattus norvegicus. Rat, brown rat, rats. Organism_taxid: 10116. Gene: glur2, gria2. Expressed in: escherichia coli. Expression_system_taxid: 562.
|
|
Resolution:
|
|
|
2.00Å
|
R-factor:
|
0.155
|
R-free:
|
0.200
|
|
|
Authors:
|
|
C.Krintel,K.Frydenvang,K.Harpsoe,M.Gajhede,J.S.Kastrup
|
|
Key ref:
|
|
C.Krintel
et al.
(2013).
Structural analysis of the positive AMPA receptor modulators CX516 and Me-CX516 in complex with the GluA2 ligand-binding domain.
Acta Crystallogr D Biol Crystallogr,
69,
1645-1652.
PubMed id:
DOI:
|
|
|
Date:
|
|
|
28-Jan-13
|
Release date:
|
09-Oct-13
|
|
|
|
|
|
|
PROCHECK
|
|
|
|
|
|
Headers
|
|
|
|
References
|
|
|
|
|
|
|
|
P19491
(GRIA2_RAT) -
Glutamate receptor 2 from Rattus norvegicus
|
|
|
|
Seq:
Struc:
|
|
|
|
883 a.a.
263 a.a.*
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Key: |
 |
PfamA domain |
|
|
 |
Secondary structure |
|
 |
CATH domain |
|
|
*
PDB and UniProt seqs differ
at 6 residue positions (black
crosses)
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
|
|
|
|
|
|
| |
|
DOI no:
|
Acta Crystallogr D Biol Crystallogr
69:1645-1652
(2013)
|
|
PubMed id:
|
|
|
|
|
|
| |
|
Structural analysis of the positive AMPA receptor modulators CX516 and Me-CX516 in complex with the GluA2 ligand-binding domain.
|
|
C.Krintel,
K.Harpsøe,
L.G.Zachariassen,
D.Peters,
K.Frydenvang,
D.S.Pickering,
M.Gajhede,
J.S.Kastrup.
|
|
|
|
|
| |
ABSTRACT
|
|
|
|
| |
|
|
Positive allosteric modulators of the ionotropic glutamate receptor A2 (GluA2)
can serve as lead compounds for the development of cognitive enhancers. Several
benzamide-type (S)-2-amino-3-(3-hydroxy-5-methyl-4-isoxazolyl)propionic acid
(AMPA) receptor modulators such as aniracetam, CX516 and CX614 have been shown
to inhibit the deactivation of AMPA receptors with a less pronounced effect on
desensitization. Despite CX516 being an extensively investigated AMPA receptor
modulator and one of the few clinically evaluated compounds, the binding mode of
CX516 to AMPA receptors has not been reported. Here, the structures of a GluA2
ligand-binding domain mutant in complex with CX516 and the 3-methylpiperidine
analogue of CX516 (Me-CX516) are reported. The structures show that the binding
modes of CX516 and Me-CX516 are similar to those of aniracetam and CX614 and
that there is limited space for substitution at the piperidine ring of CX516.
The results therefore support that CX516, like aniracetam and CX614, modulates
deactivation of AMPA receptors.
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
 |
 |
|
Links
