Loop B is a major structural component of the 5-HT3 receptor.

ABSTRACT: The 5-HT(3) receptor belongs to a family of therapeutically important neurotransmitter-gated receptors whose ligand binding sites are formed by the convergence of six peptide loops (A-F). Here we have mutated 15 amino acid residues in and around loop B of the 5-HT(3) receptor (Ser-177 to Asn-191) to Ala or a residue with similar chemical properties. Changes in [3H]granisetron binding affinity (K(d)) and 5-HT EC(50) were determined using receptors expressed in human embryonic kidney 293 cells. Substitutions at all but one residue (Thr-181) altered or eliminated binding for one or both mutants. Receptors were nonfunctional or EC(50) values were altered for all but two mutants (S182T, I190L). Homology modeling indicates that loop B contributes two residues to a hydrophobic core that faces int

SUBMITTER: Thompson AJ 

PROVIDER: S-EPMC2599823 | biostudies-literature | 2008 Dec

REPOSITORIES: biostudies-literature