Laboratory of Cellular and Molecular Neurophysiology, Porter Neuroscience Research Center, NICHD, NIH, DHHS, Bethesda, MD 20892, USA.
Neuropharmacology. 2011 Jan;60(1):126-34. doi: 10.1016/j.neuropharm.2010.06.002. Epub 2010 Jun 15.
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 site 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.
离子型谷氨酸受体配体结合域的晶体结构的可用性，加上它们在正常和患病大脑中的突触功能中的关键作用，与其他药物靶点相比，为药物研究提供了独特的选择，对于这些药物靶点，配体结合位点的原子结构尚不清楚。目前只有少数拮抗剂结构得到了解决，这些结构揭示了阻碍合理药物设计的配体特异性构象变化。在这里，我们报告了三个 kainate 受体 GluK1 拮抗剂复合物的高分辨率晶体结构，这些结构揭示了新的和意外的结合模式，突出了继续需要实验确定的受体-配体复合物。
