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	Structural basis for partial agonism in 5-HT receptors.
ジャーナル・号・ページ	Nat Struct Mol Biol, Vol. 31, Issue 4, Page 598-609, Year 2024
掲載日	2024年1月4日
著者	Kevin Felt / Madeleine Stauffer / Leslie Salas-Estrada / Peter R Guzzo / Dejian Xie / Jinkun Huang / Marta Filizola / Sudha Chakrapani /
PubMed 要旨	Hyperactivity of serotonin 3 receptors (5-HTR) underlies pathologies associated with irritable bowel syndrome and chemotherapy-induced nausea and vomiting. Setrons, a class of high-affinity ...Hyperactivity of serotonin 3 receptors (5-HTR) underlies pathologies associated with irritable bowel syndrome and chemotherapy-induced nausea and vomiting. Setrons, a class of high-affinity competitive antagonists, are used in the treatment of these conditions. Although generally effective for chemotherapy-induced nausea and vomiting, the use of setrons for treating irritable bowel syndrome has been impaired by adverse side effects. Partial agonists are now being considered as an alternative strategy, with potentially less severe side effects than full antagonists. However, a structural understanding of how these ligands work is lacking. Here, we present high-resolution cryogenic electron microscopy structures of the mouse 5-HTR in complex with partial agonists (SMP-100 and ALB-148471) captured in pre-activated and open-like conformational states. Molecular dynamics simulations were used to assess the stability of drug-binding poses and interactions with the receptor over time. Together, these studies reveal mechanisms for the functional differences between orthosteric partial agonists, full agonists and antagonists of the 5-HTR.
リンク	Nat Struct Mol Biol / PubMed:38177669
手法	EM (単粒子)
解像度	2.7 - 3.79 Å
構造データ	29409 8frw EMDB-29409, PDB-8frw: Full-length mouse 5-HT3A receptor in complex with ALB148471, pre-activated 手法: EM (単粒子) / 解像度: 2.92 Å 29410 8frx EMDB-29410, PDB-8frx: Full-length mouse 5-HT3A receptor in complex with SMP100, pre-activated 手法: EM (単粒子) / 解像度: 2.7 Å 29411 8frz EMDB-29411, PDB-8frz: Full-length mouse 5-HT3A receptor in complex with serotonin, pre-activated 手法: EM (単粒子) / 解像度: 2.75 Å 29418 8fsb EMDB-29418, PDB-8fsb: Full-length mouse 5-HT3A receptor in complex with serotonin, open-like 手法: EM (単粒子) / 解像度: 2.75 Å 29421 8fsp EMDB-29421, PDB-8fsp: Full-length mouse 5-HT3A receptor in complex with SMP100, open-like 手法: EM (単粒子) / 解像度: 3.79 Å 29422 8fsz EMDB-29422, PDB-8fsz: Full-length mouse 5-HT3A receptor in complex with ALB148471, open-like 手法: EM (単粒子) / 解像度: 3.79 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-Y7H: 5-[(1R,3S,5R)-1-azabicyclo[3.2.2]nonan-3-yl]-1,3,4,5-tetrahydro-6H-azepino[5,4,3-cd]indazol-6-one ChemComp-HOH: WATER ChemComp-Y82: 5-[(1R,3S,4R)-1-azabicyclo[2.2.2]octan-3-yl]-1,3,4,5-tetrahydro-6H-azepino[5,4,3-cd]indazol-6-one ChemComp-SRO: SEROTONIN / セロトニン / 神経伝達物質*YM
由来	mus musculus (ハツカネズミ)
キーワード	TRANSPORT PROTEIN / Partial agonist / cys-loop / pLGIC / ion channel / agonist