The availability of crystal structures for the ligand binding domains of
ionotropic glutamate receptors, combined with their key role in synaptic
function in the normal and diseased brain, offers a unique selection of targets
for pharmaceutical research compared to other drug targets for which the atomic
structure of the ligand binding sites is not known. Currently only a few
antagonist structures have been solved, and these reveal ligand specific
conformational changes that hinder rational drug design. Here we report high
resolution crystal structures for three kainate receptor GluK1 antagonist
complexes which reveal new and unexpected modes of binding, highlighting the
continued need for experimentally determined receptor-ligand complexes.
