直接的结构洞察 GABA 受体药理学。
Direct Structural Insights into GABA Receptor Pharmacology.
机构信息
Department of Neuroscience, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Department of Neuroscience, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
出版信息
Trends Biochem Sci. 2021 Jun;46(6):502-517. doi: 10.1016/j.tibs.2021.01.011. Epub 2021 Mar 3.
Abstract
GABA receptors are pentameric ligand-gated ion channels that mediate most fast neuronal inhibition in the brain. In addition to their important physiological roles, they are noteworthy in their rich pharmacology; prominent drugs used for anxiety, insomnia, and general anesthesia act through positive modulation of GABA receptors. Direct structural information for how these drugs work was absent until recently. Efforts in structural biology over the past few years have revealed how important drug classes and natural products interact with the GABA receptor, providing a foundation for studies in dynamics and structure-guided drug design. Here, we review recent developments in GABA receptor structural pharmacology, focusing on subunit assemblies of the receptor found at synapses.
摘要
GABA 受体是五聚体配体门控离子通道，介导大脑中大多数快速神经元抑制。除了它们重要的生理作用外，它们丰富的药理学也值得注意；用于焦虑、失眠和全身麻醉的重要药物通过 GABA 受体的正调控起作用。直到最近，这些药物如何发挥作用的直接结构信息还不存在。过去几年结构生物学领域的努力揭示了重要的药物类别和天然产物如何与 GABA 受体相互作用，为动力学研究和基于结构的药物设计提供了基础。在这里，我们回顾了 GABA 受体结构药理学的最新进展，重点介绍了突触处发现的受体亚基组装。
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