Kuryatov A, Laube B, Betz H, Kuhse J
Abteilung Neurochemie, Max-Planck-Institut für Hirnforschung, Frankfurt, Federal Republic of Germany.
Neuron. 1994 Jun;12(6):1291-300. doi: 10.1016/0896-6273(94)90445-6.
Activation of the NMDA subtype of ionotropic glutamate receptors requires binding of both L-glutamate and the coagonist glycine. Site-directed mutagenesis of the NMDAR1 (NR1) subunit revealed that aromatic residues at positions 390, 392, and 466 are crucial determinants of glycine binding. Glutamate efficacy was little affected by mutations at these positions; however, inhibition of channel gating by the glycine antagonist 7-chlorokynurenic acid was drastically reduced. In addition, glutamine (Q387), valine (V666), and serine (S669) substitutions were found to reduce glycine efficacy. Since the mutated residues correspond to positions forming the binding site of homologous bacterial amino acid-binding proteins, a common amino acid-binding fold appears to be conserved from prokaryotic periplasmic proteins to glutamate receptors in the mammalian brain.
离子型谷氨酸受体的NMDA亚型的激活需要L-谷氨酸和共激动剂甘氨酸的结合。对NMDAR1（NR1）亚基进行定点诱变发现，第390、392和466位的芳香族残基是甘氨酸结合的关键决定因素。这些位置的突变对谷氨酸的效力影响很小；然而，甘氨酸拮抗剂7-氯犬尿氨酸对通道门控的抑制作用大幅降低。此外，发现谷氨酰胺（Q387）、缬氨酸（V666）和丝氨酸（S669）的取代会降低甘氨酸的效力。由于突变的残基对应于形成同源细菌氨基酸结合蛋白结合位点的位置，从原核周质蛋白到哺乳动物大脑中的谷氨酸受体，一种常见的氨基酸结合折叠似乎是保守的。
