EMDB/PDB/SASBDBから引用されている文献のデータベース

キーワード
構造解析手法	All X線回折 NMR 電子顕微鏡小角散乱中性子線回折線維回折粉末回折赤外分光 EPR FRET 理論モデルハイブリッド
著者・登録者
ジャーナル
IF	>30 >20 >10 >5 all

タイトル	Molecular basis for substrate recognition and transport of human GABA transporter GAT1.
ジャーナル・号・ページ	Nat Struct Mol Biol, Vol. 30, Issue 7, Page 1012-1022, Year 2023
掲載日	2023年7月3日
著者	Angqi Zhu / Junhao Huang / Fang Kong / Jiaxin Tan / Jianlin Lei / Yafei Yuan / Chuangye Yan /
PubMed 要旨	γ-Aminobutyric acid (GABA), an important inhibitory neurotransmitter in the central nervous system, is recycled through specific GABA transporters (GATs). GAT1, which is mainly expressed in the ...γ-Aminobutyric acid (GABA), an important inhibitory neurotransmitter in the central nervous system, is recycled through specific GABA transporters (GATs). GAT1, which is mainly expressed in the presynaptic terminals of axons, is a potential drug target of neurological disorders due to its essential role in GABA transport. Here we report four cryogenic electron microscopy structures of human GAT1, at resolutions of 2.2-3.2 Å. GAT1 in substrate-free form or in complex with the antiepileptic drug tiagabine exhibits an inward-open conformation. In the presence of GABA or nipecotic acid, inward-occluded structures are captured. The GABA-bound structure reveals an interaction network bridged by hydrogen bonds and ion coordination for GABA recognition. The substrate-free structure unwinds the last helical turn of transmembrane helix TM1a to release sodium ions and substrate. Complemented by structure-guided biochemical analyses, our studies reveal detailed mechanism of GABA recognition and transport, and elucidate mode of action of the inhibitors, nipecotic acid and tiagabine.
リンク	Nat Struct Mol Biol / PubMed:37400655
手法	EM (単粒子)
解像度	2.2 - 3.2 Å
構造データ	33671 7y7v EMDB-33671, PDB-7y7v: Cryo-EM structure of human apo GABA transporter GAT1 in an inward-open state 手法: EM (単粒子) / 解像度: 2.2 Å 33672 7y7w EMDB-33672, PDB-7y7w: Cryo-EM structure of human GABA transporter GAT1 bound with GABA in NaCl solution in an inward-occluded state at 2.4 angstrom 手法: EM (単粒子) / 解像度: 2.4 Å 33674 7y7y EMDB-33674, PDB-7y7y: Cryo-EM structure of human GABA transporter GAT1 bound with nipecotic acid in NaCl solution in an inward-occluded state at 2.4 angstrom 手法: EM (単粒子) / 解像度: 2.4 Å 33675 7y7z EMDB-33675, PDB-7y7z: Cryo-EM structure of human GABA transporter GAT1 bound with tiagabine in NaCl solution in an inward-open state at 3.2 angstrom 手法: EM (単粒子) / 解像度: 3.2 Å
化合物	ChemComp-NAG: 2-acetamido-2-deoxy-beta-D-glucopyranose / N-アセチル-β-D-グルコサミン ChemComp-CL: Unknown entry / クロリド ChemComp-HOH: WATER ChemComp-ABU: GAMMA-AMINO-BUTANOIC ACID / GABA ChemComp-NA: Unknown entry / ナトリウムカチオン ChemComp-ID7: (3R)-piperidine-3-carboxylic acid / (R)-ニペコチン酸 ChemComp-TGI: Tiagabine / チアガビン / 薬剤*YM
由来	homo sapiens (ヒト)
キーワード	TRANSPORT PROTEIN / GABA transporter / GAT1 / Nipecotic acid / Tiagabine / Neurotransmitter / SLC6A1 / SLC6A1.