A mutation in the glycine binding pocket of the N-methyl-D-aspartate receptor NR1 subunit alters agonist efficacy.
Alanine 714 of the NMDA receptor NR1 subunit resides in the glycine binding pocket. The Ala714Leu mutation substantially shifts glycine affinity, but here no effect on antagonism by DCK is detected. Ala714Leu is also found to limit the efficacy of a partial agonist without altering its apparent affinity. The differential sensitivity of Ala714Leu to glycine agonists suggests that alanine 714 may be an intermediary in transducing the ligand binding signal.
Wood
M W
MW
Department of Pharmacology and Cancer Biology, Duke University Medical Center, PO Box 3813, Durham, NC 27710, USA.
VanDongen
H M
HM
VanDongen
A M
AM
D000818:Animals; D001665:Binding Sites / Q000235:genetics; D001667:Binding, Competitive / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D018690:Excitatory Amino Acid Agonists / Q000378:metabolism*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005260:Female; D005998:Glycine / Q000235:genetics / Q000378:metabolism*; D007736:Kynurenic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D051379:Mice; D009154:Mutation; D009865:Oocytes / Q000187:drug effects / Q000378:metabolism; D011760:Pyrrolidinones / Q000494:pharmacology; D016194:Receptors, N-Methyl-D-Aspartate / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014982:Xenopus laevis
D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D011760:Pyrrolidinones; D016194:Receptors, N-Methyl-D-Aspartate; C001369:1-hydroxy-3-amino-2-pyrrolidone; D007736:Kynurenic Acid; C066192:5,7-dichlorokynurenic acid; D005998:Glycine