CaltechAUTHORS
  A Caltech Library Service

Probing the Mg^(2+) Blockade Site of an N-Methyl-d-aspartate (NMDA) Receptor with Unnatural Amino Acid Mutagenesis

McMenimen, Kathryn A. and Petersson, E. James and Lester, Henry A. and Dougherty, Dennis A. (2006) Probing the Mg^(2+) Blockade Site of an N-Methyl-d-aspartate (NMDA) Receptor with Unnatural Amino Acid Mutagenesis. ACS Chemical Biology, 1 (4). pp. 227-234. ISSN 1554-8929. doi:10.1021/cb6000944. https://resolver.caltech.edu/CaltechAUTHORS:20170201-140122486

[img] MS Word (Probing the Mg2+ Blockade Site of an N-Methyl-d-aspartate (NMDA) ...) - Supplemental Material
See Usage Policy.

484kB

Use this Persistent URL to link to this item: https://resolver.caltech.edu/CaltechAUTHORS:20170201-140122486

Abstract

The N-methyl-d-aspartate (NMDA) receptor plays a central role in learning and memory in the mammalian CNS. At normal neuronal resting membrane potentials, the pore of this glutamate-gated ion channel is blocked by a Mg^(2+) ion. Previous work suggests that the Mg^(2+) binding site is quite novel, involving several asparagine residues and a cation–π interaction between Mg^(2+) and a conserved tryptophan in the pore. Using unnatural amino acid mutagenesis, we show that no such cation–π interaction exists. The implicated tryptophan instead appears to play a structural role that can only be fulfilled by a rigid, flat, hydrophobic residue. This is the first demonstration of unnatural amino acid incorporation in the NMDA receptor, and it opens the way for future investigations of this pivotal neuroreceptor.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.1021/cb6000944DOIArticle
http://pubs.acs.org/doi/full/10.1021/cb6000944PublisherArticle
http://pubs.acs.org/doi/suppl/10.1021/cb6000944PublisherSupporting Information
ORCID:
AuthorORCID
Petersson, E. James0000-0003-3854-9210
Lester, Henry A.0000-0002-5470-5255
Dougherty, Dennis A.0000-0003-1464-2461
Additional Information:© 2006 American Chemical Society. Received 1 March 2006. Date accepted 21 April 2006. Published online 12 May 2006. Published in print 1 May 2006. We thank K. Williams for the NMDA receptor subunit clones and C. Waters for use of the Beckman Institute Biological Imaging Center. This work was supported by grants from the National Institutes of Health (NS-34407, and NS-11756).
Funders:
Funding AgencyGrant Number
NIHNS-34407
NIHNS-11756
Issue or Number:4
DOI:10.1021/cb6000944
Record Number:CaltechAUTHORS:20170201-140122486
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20170201-140122486
Official Citation:Probing the Mg2+ Blockade Site of an N-Methyl-d-aspartate (NMDA) Receptor with Unnatural Amino Acid Mutagenesis Kathryn A. McMenimen, E. James Petersson, Henry A. Lester, and Dennis A. Dougherty ACS Chemical Biology 2006 1 (4), 227-234 DOI: 10.1021/cb6000944
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:73944
Collection:CaltechAUTHORS
Deposited By: Ruth Sustaita
Deposited On:01 Feb 2017 23:02
Last Modified:11 Nov 2021 05:23

Repository Staff Only: item control page