The DOI matches its Crossref record; 47 of the 48 references it cites were found in a registry or an index.
Identification and Mechanism of Action of Two Histidine Residues Underlying High-Affinity Zn2+ Inhibition of the NMDA Receptor
Open accessAbstract
Zinc (Zn2+) inhibition of N-methyl-D-aspartate receptor (NMDAR) activity involves both voltage-independent and voltage-dependent components. Recombinant NR1/NR2A and NR1/NR2B receptors exhibit similar voltage-dependent block, but voltage-independent Zn2+ inhibition occurs with much higher affinity for NR1/NR2A than NR1/NR2B receptors (nanomolar versus micromolar IC50, respectively). Here, we show that two neighboring histidine residues on NR2A represent the critical determinant (termed the "short spacer") for high-affinity, voltage-independent Zn2+ inhibition using the Xenopus oocyte expression system and site-directed mutagenesis. Mutation of either one of these two histidine residues (H42 and H44) in the extracellular N-terminal domain of NR2A shifted the IC50 for high-affinity Zn2+ inhibition approximately 200-fold without affecting the EC50 of the coagonists NMDA and glycine. We suggest that the mechanism of high-affinity Zn2+ inhibition on the NMDAR involves enhancement of proton inhibition.
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“Of note, even transient GSH deficits are sufficient to induce NMDAR hypofunction 70 .”
From Linking early-life NMDAR hypofunction and oxidative stress in schizophrenia pathogenesis (2016) · cites this paper as [70]
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Structure, Function, and Pharmacology of Glutamate Receptor Ion Channels
Hansen, K. B., Wollmuth, L. P., Bowie, D., Furukawa, H., Menniti, F. S., Sobolevsky, A. I., Swanson, G. T., Swanger, S. A., Greger, I. H., Nakagawa, T., et al. (2021) · Pharmacological Reviews · doi:10.1124/pharmrev.120.000131 · Cited by 686
Metadata
- Authors
- Choi, Y.-B., & Lipton, S. A.
- Affiliations
- Brigham and Women's Hospital (US)
- Corresponding author
- Lipton, Stuart A
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 1999-05
- Volume
- 23
- Issue
- 1
- Pages
- 171-180
- ISSN
- 0896-6273 (ISSN-L)
- OpenAlex
- W1970564284
- Cited by
- 180
- References
- 48
- Citations by year
- 2025: 2 · 2024: 1 · 2022: 4 · 2021: 2 · 2020: 4 · 2019: 3 · 2018: 7 · 2017: 4 · 2016: 8 · 2015: 5 · 2014: 10 · 2013: 4 · 2012: 12
- FWCI
- 3.71
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Neuron (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Eye Institute (R01EY005477)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (P01HD029587)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Amino Acid Enzymes and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
- Keywords
- zinc inhibition, NMDA receptor, NR2A subunit, histidine residues, voltage-dependent block, proton inhibition, site-directed mutagenesis
- MeSH terms
- Animals, Diethyl Pyrocarbonate, Female, Histidine, Mutation, Oocytes, Xenopus laevis, Zinc, Receptors, N-Methyl-D-Aspartate, Patch-Clamp Techniques, Protein Isoforms
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