An alanine residue in the M3-M4 linker lines the glycine binding pocket of the N-methyl-D-aspartate receptor.

Published

Journal Article

While attempting to map a central region in the M3-M4 linker of the N-methyl-D-aspartate receptor NR1 subunit, we found that mutation of a single position, Ala-714, greatly reduced the apparent affinity for glycine. Proximal N-glycosylation localized this region to the extracellular space. Glycine affinities of additional Ala-714 mutations correlated with side chain volume. Substitution of alanine 714 with cysteine did not alter glycine sensitivity, although this mutant was rapidly inhibited by dithionitrobenzoate. Glycine protected the A714C mutant from modification by dithionitrobenzoate, whereas the co-agonist L-glutamate was ineffective. These experiments place Ala-714 in the glycine binding pocket of the N-methyl-D-aspartate receptor, a determination not predicted by previous structural models based on bacterial periplasmic binding protein homology.

Full Text

Duke Authors

Cited Authors

  • Wood, MW; VanDongen, HM; VanDongen, AM

Published Date

  • February 7, 1997

Published In

Volume / Issue

  • 272 / 6

Start / End Page

  • 3532 - 3537

PubMed ID

  • 9013601

Pubmed Central ID

  • 9013601

International Standard Serial Number (ISSN)

  • 0021-9258

Digital Object Identifier (DOI)

  • 10.1074/jbc.272.6.3532

Language

  • eng

Conference Location

  • United States