Small-molecule positive allosteric modulation of homomeric kainate receptors GluK1-3: development of screening assays and insight into GluK3 structure.

Kainate receptors X-ray crystallography calcium-sensitive fluorescence-based assays electron microscopy molecular dynamics simulations

Journal

The FEBS journal
ISSN: 1742-4658
Titre abrégé: FEBS J
Pays: England
ID NLM: 101229646

Informations de publication

Date de publication:
25 Dec 2023
Historique:
revised: 20 10 2023
received: 06 07 2023
accepted: 29 11 2023
medline: 25 12 2023
pubmed: 25 12 2023
entrez: 25 12 2023
Statut: aheadofprint

Résumé

The kainate receptors GluK1-3 (glutamate receptor ionotropic, kainate receptors 1-3) belong to the family of ionotropic glutamate receptors and are essential for fast excitatory neurotransmission in the brain, and are associated with neurological and psychiatric diseases. How these receptors can be modulated by small-molecule agents is not well understood, especially for GluK3. We show that the positive allosteric modulator BPAM344 can be used to establish robust calcium-sensitive fluorescence-based assays to test agonists, antagonists and positive allosteric modulators of GluK1-3. The half maximal effective concentration (EC

Identifiants

pubmed: 38145505
doi: 10.1111/febs.17046
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Informations de copyright

This article is protected by copyright. All rights reserved.

Auteurs

Yasmin Bay (Y)

Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, DK-2100, Copenhagen, Denmark.

Raminta Venskutonytė (R)

Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, DK-2100, Copenhagen, Denmark.
Present address: Department of Experimental Medical Science, Lund University, 221 00, Lund, Sweden.

Stine M Frantsen (SM)

Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, DK-2100, Copenhagen, Denmark.

Thor S Thorsen (TS)

Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, DK-2100, Copenhagen, Denmark.

Maria Musgaard (M)

Department of Biochemistry, University of Oxford, Oxford, United Kingdom.
Present address: OMass Therapeutics, Oxford, United Kingdom.

Karla Frydenvang (K)

Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, DK-2100, Copenhagen, Denmark.

Pierre Francotte (P)

Department of Medicinal Chemistry, Center for Interdisciplinary Research on Medicines (CIRM), University of Liège, Liège, Belgium.

Bernard Pirotte (B)

Department of Medicinal Chemistry, Center for Interdisciplinary Research on Medicines (CIRM), University of Liège, Liège, Belgium.

Philip C Biggin (PC)

Department of Biochemistry, University of Oxford, Oxford, United Kingdom.

Anders S Kristensen (AS)

Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, DK-2100, Copenhagen, Denmark.

Thomas Boesen (T)

Danish Research Institute of Translational Neuroscience-DANDRITE, Nordic-EMBL Partnership for Molecular Medicine, Department of Molecular Biology and Genetics, Aarhus University, DK-8000, Aarhus, Denmark.

Darryl S Pickering (DS)

Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, DK-2100, Copenhagen, Denmark.

Michael Gajhede (M)

Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, DK-2100, Copenhagen, Denmark.

Jette S Kastrup (JS)

Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, DK-2100, Copenhagen, Denmark.

Classifications MeSH