Premium
Modeling the Alcohol Binding Site of the NMDA Receptor Using the GluA2‐receptor Structure (LB110)
Author(s) -
Ali Moid,
Gundamraj Shivani,
Kaur Tejas,
Morris Sarah,
Puri Simar,
Singh Ricky,
Singh Vipul,
SmithFeinburg Lee,
Wang Leah,
Tuinstra Robbyn,
Peoples Robert
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.lb110
Subject(s) - nmda receptor , heterotetramer , receptor , glutamate receptor , ampa receptor , chemistry , neuroscience , ion channel , pharmacology , microbiology and biotechnology , biochemistry , medicine , biology , protein subunit , gene
According to the National Institute of Alcohol Abuse and Alcoholism, about 18 million people have an alcohol abuse disorder. Alcohol binds to the N‐Methyl‐D‐aspartate Receptor (NMDA) receptor, inhibiting cognition, short‐term memory formation, motor coordination, and overall regular CNS function. The Brookfield Academy SMART (Students Modeling A Research Topic) Team used 3D printing technology to model the alcohol binding site on the NMDA receptor. This receptor is an ion channel in CNS neurons. Binding of the neurotransmitter, glutamate, allows the passage of calcium and sodium ions through the channel, thus controlling multiple intracellular signaling pathways. Alcohol inhibits the gating of the receptor, preventing the flow of ions, leading to the symptoms of intoxication. The NMDA receptor is a heterotetramer, containing two GluN1 and two GluN2A subunits. Alcohol binds to the transmembrane domain of the receptor, interacting with the amino acids Gly638, Phe639, Phe639, Leu819, and Met818 (of subunit GluN1) and Met 823, Phe636, Leu824 and Phe637 (on GluN2A). Site‐directed mutagenesis studies have identified the importance of these residues. Mutations in the same position on different subunits can drastically modulate the inhibition of the receptor by alcohol. Further understanding of the NMDA receptor mechanisms could lead to treatment for long‐term alcohol abuse. Grant Funding Source : The SMART team program is supported by a grant from NIH‐CTSA.