Structural insights into phenylethanolamines high-affinity binding site in NR2B from binding and molecular modeling studies.

ABSTRACT:

Background

Phenylethanolamines selectively bind to NR2B subunit-containing N-methyl-D-aspartate-subtype of ionotropic glutamate receptors and negatively modulate receptor activity. To investigate the structural and functional properties of the ifenprodil binding domain on the NR2B protein, we have purified a soluble recombinant rat NR2B protein fragment comprising the first ~400 amino acid amino-terminal domain (ATD2B) expressed in E. coli. Spectral measurements on refolded ATD2B protein demonstrated specific binding to ifenprodil. We have used site-directed mutagenesis, circular dichroism spectroscopy and molecular modeling to obtain structural information on the interactions between critical amino acid residues and ifenprodil of our soluble refolded ATD2B proteins. Ligand-induced

SUBMITTER: Ng FM 

PROVIDER: S-EPMC2603005 | biostudies-literature | 2008 Nov

REPOSITORIES: biostudies-literature