Molecular mechanism of flop selectivity and subsite recognition for an AMPA receptor allosteric modulator: structures of GluA2 and GluA3 in complexes with PEPA.

ABSTRACT: Glutamate receptors are important potential drug targets for cognitive enhancement and the treatment of schizophrenia in part because they are the most prevalent excitatory neurotransmitter receptors in the vertebrate central nervous system. One approach to the application of therapeutic agents to the AMPA subtype of glutamate receptors is the use of allosteric modulators, which promote dimerization by binding to a dimer interface thereby reducing the degree of desensitization and deactivation. AMPA receptors exist in two alternatively spliced variants (flip and flop) that differ in desensitization and receptor activation profiles. Most of the structural information about modulators of the AMPA receptor targets the flip subtype. We report here the crystal structure of the flop-selective al

SUBMITTER: Ahmed AH 

PROVIDER: S-EPMC3072023 | biostudies-literature | 2010 Apr

REPOSITORIES: biostudies-literature