Structural basis of subtype-selective competitive antagonism for GluN2C/2D-containing NMDA receptors

Jue Xiang Wang; Mark W. Irvine; Erica S. Burnell; Kiran Sapkota; Robert J. Thatcher; Minjun Li; Noriko Simorowski; Arturas Volianskis; Graham L. Collingridge; Daniel T. Monaghan; David E. Jane; Hiro Furukawa

doi:10.1038/s41467-020-14321-0

Nature Communications (Jan 2020)

Structural basis of subtype-selective competitive antagonism for GluN2C/2D-containing NMDA receptors

Jue Xiang Wang,
Mark W. Irvine,
Erica S. Burnell,
Kiran Sapkota,
Robert J. Thatcher,
Minjun Li,
Noriko Simorowski,
Arturas Volianskis,
Graham L. Collingridge,
Daniel T. Monaghan,
David E. Jane,
Hiro Furukawa

Affiliations

Jue Xiang Wang: WM Keck Structural Biology Laboratory, Cold Spring Harbor Laboratory
Mark W. Irvine: Glutamate Research Group, School of Physiology, Pharmacology and Neuroscience, University of Bristol
Erica S. Burnell: Glutamate Research Group, School of Physiology, Pharmacology and Neuroscience, University of Bristol
Kiran Sapkota: Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center
Robert J. Thatcher: Glutamate Research Group, School of Physiology, Pharmacology and Neuroscience, University of Bristol
Minjun Li: WM Keck Structural Biology Laboratory, Cold Spring Harbor Laboratory
Noriko Simorowski: WM Keck Structural Biology Laboratory, Cold Spring Harbor Laboratory
Arturas Volianskis: Centre for Neuroscience and Trauma, Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London
Graham L. Collingridge: Glutamate Research Group, School of Physiology, Pharmacology and Neuroscience, University of Bristol
Daniel T. Monaghan: Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center
David E. Jane: Glutamate Research Group, School of Physiology, Pharmacology and Neuroscience, University of Bristol
Hiro Furukawa: WM Keck Structural Biology Laboratory, Cold Spring Harbor Laboratory

DOI: https://doi.org/10.1038/s41467-020-14321-0
Journal volume & issue: Vol. 11, no. 1
pp. 1 – 14

Abstract

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Selectively inhibiting N-Methyl-D-aspartate receptors (NMDARs) containing the GluN2C/2D subunits has been challenging. Here, using electrophysiology and X-ray crystallography, authors show that compounds UBP791 and UBP1700 show over 40- and 50-fold selectivity for GluN2C/2D compared to GluN2A.

Published in Nature Communications

ISSN: 2041-1723 (Online)
Publisher: Nature Portfolio
Country of publisher: United Kingdom
LCC subjects: Science
Website: https://www.nature.com/ncomms/

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