Exploring the GluR2 ligand-binding core in complex with the bicyclical AMPA analogue (S)-4-AHCP

Research output: Contribution to journal › Journal article › Research › peer-review

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Exploring the GluR2 ligand-binding core in complex with the bicyclical AMPA analogue (S)-4-AHCP. / Nielsen, Bettina B; Pickering, Darryl S; Greenwood, Jeremy R; Brehm, Lotte; Gajhede, Michael; Schousboe, Arne; Kastrup, Jette S.

In: FEBS Journal, Vol. 272, No. 7, 2005, p. 1639-48.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Nielsen, BB, Pickering, DS, Greenwood, JR, Brehm, L, Gajhede, M, Schousboe, A & Kastrup, JS 2005, 'Exploring the GluR2 ligand-binding core in complex with the bicyclical AMPA analogue (S)-4-AHCP', FEBS Journal, vol. 272, no. 7, pp. 1639-48. https://doi.org/10.1111/j.1742-4658.2005.04583.x

APA

Nielsen, B. B., Pickering, D. S., Greenwood, J. R., Brehm, L., Gajhede, M., Schousboe, A., & Kastrup, J. S. (2005). Exploring the GluR2 ligand-binding core in complex with the bicyclical AMPA analogue (S)-4-AHCP. FEBS Journal, 272(7), 1639-48. https://doi.org/10.1111/j.1742-4658.2005.04583.x

Vancouver

Nielsen BB, Pickering DS, Greenwood JR, Brehm L, Gajhede M, Schousboe A et al. Exploring the GluR2 ligand-binding core in complex with the bicyclical AMPA analogue (S)-4-AHCP. FEBS Journal. 2005;272(7):1639-48. https://doi.org/10.1111/j.1742-4658.2005.04583.x

Author

Nielsen, Bettina B ; Pickering, Darryl S ; Greenwood, Jeremy R ; Brehm, Lotte ; Gajhede, Michael ; Schousboe, Arne ; Kastrup, Jette S. / Exploring the GluR2 ligand-binding core in complex with the bicyclical AMPA analogue (S)-4-AHCP. In: FEBS Journal. 2005 ; Vol. 272, No. 7. pp. 1639-48.

Bibtex

@article{948882f06e8e11df928f000ea68e967b,

title = "Exploring the GluR2 ligand-binding core in complex with the bicyclical AMPA analogue (S)-4-AHCP",

abstract = "The X-ray structure of the ionotropic GluR2 ligand-binding core (GluR2-S1S2J) in complex with the bicyclical AMPA analogue (S)-2-amino-3-(3-hydroxy-7,8-dihydro-6H-cyclohepta[d]-4-isoxazolyl)propionic acid [(S)-4-AHCP] has been determined, as well as the binding pharmacology of this construct and of the full-length GluR2 receptor. (S)-4-AHCP binds with a glutamate-like binding mode and the ligand adopts two different conformations. The K(i) of (S)-4-AHCP at GluR2-S1S2J was determined to be 185 +/- 29 nM and at full-length GluR2(R)o it was 175 +/- 8 nM. (S)-4-AHCP appears to elicit partial agonism at GluR2 by inducing an intermediate degree of domain closure (17 degrees). Also, functionally (S)-4-AHCP has an efficacy of 0.38 at GluR2(Q)i, relative to (S)-glutamate. The proximity of bound (S)-4-AHCP to domain D2 prevents full D1-D2 domain closure, which is limited by steric repulsion, especially between Leu704 and the ligand.",

author = "Nielsen, {Bettina B} and Pickering, {Darryl S} and Greenwood, {Jeremy R} and Lotte Brehm and Michael Gajhede and Arne Schousboe and Kastrup, {Jette S}",

note = "Keywords: Alanine; Animals; Cells, Cultured; Female; Isoxazoles; Ligands; Receptors, AMPA; Spodoptera; Xenopus laevis",

year = "2005",

doi = "10.1111/j.1742-4658.2005.04583.x",

language = "English",

volume = "272",

pages = "1639--48",

journal = "F E B S Journal",

issn = "1742-464X",

publisher = "Wiley-Blackwell",

number = "7",

}

RIS

TY - JOUR

T1 - Exploring the GluR2 ligand-binding core in complex with the bicyclical AMPA analogue (S)-4-AHCP

AU - Nielsen, Bettina B

AU - Pickering, Darryl S

AU - Greenwood, Jeremy R

AU - Brehm, Lotte

AU - Gajhede, Michael

AU - Schousboe, Arne

AU - Kastrup, Jette S

N1 - Keywords: Alanine; Animals; Cells, Cultured; Female; Isoxazoles; Ligands; Receptors, AMPA; Spodoptera; Xenopus laevis

PY - 2005

Y1 - 2005

N2 - The X-ray structure of the ionotropic GluR2 ligand-binding core (GluR2-S1S2J) in complex with the bicyclical AMPA analogue (S)-2-amino-3-(3-hydroxy-7,8-dihydro-6H-cyclohepta[d]-4-isoxazolyl)propionic acid [(S)-4-AHCP] has been determined, as well as the binding pharmacology of this construct and of the full-length GluR2 receptor. (S)-4-AHCP binds with a glutamate-like binding mode and the ligand adopts two different conformations. The K(i) of (S)-4-AHCP at GluR2-S1S2J was determined to be 185 +/- 29 nM and at full-length GluR2(R)o it was 175 +/- 8 nM. (S)-4-AHCP appears to elicit partial agonism at GluR2 by inducing an intermediate degree of domain closure (17 degrees). Also, functionally (S)-4-AHCP has an efficacy of 0.38 at GluR2(Q)i, relative to (S)-glutamate. The proximity of bound (S)-4-AHCP to domain D2 prevents full D1-D2 domain closure, which is limited by steric repulsion, especially between Leu704 and the ligand.

AB - The X-ray structure of the ionotropic GluR2 ligand-binding core (GluR2-S1S2J) in complex with the bicyclical AMPA analogue (S)-2-amino-3-(3-hydroxy-7,8-dihydro-6H-cyclohepta[d]-4-isoxazolyl)propionic acid [(S)-4-AHCP] has been determined, as well as the binding pharmacology of this construct and of the full-length GluR2 receptor. (S)-4-AHCP binds with a glutamate-like binding mode and the ligand adopts two different conformations. The K(i) of (S)-4-AHCP at GluR2-S1S2J was determined to be 185 +/- 29 nM and at full-length GluR2(R)o it was 175 +/- 8 nM. (S)-4-AHCP appears to elicit partial agonism at GluR2 by inducing an intermediate degree of domain closure (17 degrees). Also, functionally (S)-4-AHCP has an efficacy of 0.38 at GluR2(Q)i, relative to (S)-glutamate. The proximity of bound (S)-4-AHCP to domain D2 prevents full D1-D2 domain closure, which is limited by steric repulsion, especially between Leu704 and the ligand.

U2 - 10.1111/j.1742-4658.2005.04583.x

DO - 10.1111/j.1742-4658.2005.04583.x

M3 - Journal article

C2 - 15794751

VL - 272

SP - 1639

EP - 1648

JO - F E B S Journal

JF - F E B S Journal

SN - 1742-464X

IS - 7

ER -

ID: 20122569