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	Mechanisms of transport and analgesic compounds recognition by glycine transporter 2.
ジャーナル・号・ページ	Proc Natl Acad Sci U S A, Vol. 122, Issue 48, Page e2506722122, Year 2025
掲載日	2025年12月2日
著者	Yuhang Wang / Jiawei Su / Jun Zhao / Renjie Li / Qinru Bai / Hongyi Song / Yufei Meng / Qiao Ma / Yan Zhao /
PubMed 要旨	Glycine transporter 2 (GlyT2) regulates inhibitory glycinergic neurotransmission, and its inhibition potentiates glycinergic signaling, which is a promising strategy for managing neuropathic pain. ...Glycine transporter 2 (GlyT2) regulates inhibitory glycinergic neurotransmission, and its inhibition potentiates glycinergic signaling, which is a promising strategy for managing neuropathic pain. This study presents high-resolution structures of GlyT2 in its apo state and in complexes with the substrate glycine, analgesic inhibitors, captured in three functional states: outward-facing, occluded, and inward-facing. The glycine-bound structure reveals the binding mode of the substrate, Na and Cl. Specifically, we identified the Na3 binding site, offering fundamental insights into Na/Cl coupled substrate binding and conformational changes. Moreover, we clearly elucidate a previously unseen allosteric binding pocket for the lipid-based oleoyl-D-lysine, which acts as a wedge to stabilize GlyT2 in the outward-facing conformation and prevents its transition. Furthermore, the complex structures with small compounds ALX1393, opiranserin, and ORG25543 reveal their competitive and allosteric inhibition mechanisms. Overall, our study provides a solid foundation for understanding glycine reuptake mechanisms and developing effective and safer analgesic agents.
リンク	Proc Natl Acad Sci U S A / PubMed:41284875 / PubMed Central
手法	EM (単粒子)
解像度	2.8 - 3.8 Å
構造データ	62420 9km2 EMDB-62420, PDB-9km2: Cryo-EM structure of apo glycine transporter 2 in inward-facing state 手法: EM (単粒子) / 解像度: 3.8 Å 62421 9km3 EMDB-62421, PDB-9km3: Cryo-EM structure of glycine transporter 2 in complex with substrate glycine 手法: EM (単粒子) / 解像度: 2.9 Å 62422 9km4 EMDB-62422, PDB-9km4: Cryo-EM structure of glycine transporter 2 in complex with oleoyl-D-lysine 手法: EM (単粒子) / 解像度: 3.2 Å 62423 9km5 EMDB-62423, PDB-9km5: Cryo-EM structure of Xenopus tropicalis glycine transporter 2 in complex with ALX1393 手法: EM (単粒子) / 解像度: 3.5 Å 62424 9km7 EMDB-62424, PDB-9km7: Cryo-EM structure of glycine transporter 2 in complex with ORG25543 手法: EM (単粒子) / 解像度: 2.8 Å 62425 9km8 EMDB-62425, PDB-9km8: Cryo-EM structure of Xenopus tropicalis glycine transporter 2 in complex with VVZ149 手法: EM (単粒子) / 解像度: 3.5 Å
化合物	ChemComp-CLR: CHOLESTEROL / コレステロ-ル ChemComp-GLY: GLYCINE / グリシン ChemComp-NA: Unknown entry / ナトリウムカチオン ChemComp-CL: Unknown entry / クロリド ChemComp-HOH: WATER ChemComp-DLY: D-LYSINE / D-リシン ChemComp-OLA: OLEIC ACID / オレイン酸 PDB-1ez0: CRYSTAL STRUCTURE OF THE NADP+ DEPENDENT ALDEHYDE DEHYDROGENASE FROM VIBRIO HARVEYI. PDB-1ef1: CRYSTAL STRUCTURE OF THE MOESIN FERM DOMAIN/TAIL DOMAIN COMPLEX PDB-1ef3: FIDARESTAT BOUND TO HUMAN ALDOSE REDUCTASE
由来	xenopus tropicalis (ネッタイツメガエル)
キーワード	MEMBRANE PROTEIN / GLYT2; PROTEIN STRUCTURE