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 insights into the mechanisms of urea permeation and distinct inhibition modes of urea transporters.
ジャーナル・号・ページ	Nat Commun, Vol. 15, Issue 1, Page 10226, Year 2024
掲載日	2024年11月26日
著者	Shen-Ming Huang / Zhi-Zhen Huang / Lei Liu / Meng-Yao Xiong / Chao Zhang / Bo-Yang Cai / Ming-Wei Wang / Kui Cai / Ying-Li Jia / Jia-Le Wang / Ming-Hui Zhang / Yi-He Xie / Min Li / Hang Zhang / Cheng-Hao Weng / Xin Wen / Zhi Li / Ying Sun / Fan Yi / Zhao Yang / Peng Xiao / Fan Yang / Xiao Yu / Lu Tie / Bao-Xue Yang / Jin-Peng Sun /
PubMed 要旨	Urea's transmembrane transport through urea transporters (UT) is a fundamental physiological behavior for life activities. Here, we present 11 cryo-EM structures of four UT members in resting states, ...Urea's transmembrane transport through urea transporters (UT) is a fundamental physiological behavior for life activities. Here, we present 11 cryo-EM structures of four UT members in resting states, urea transport states, or inactive states bound with synthetic competitive, uncompetitive or noncompetitive inhibitor. Our results indicate that the binding of urea via a conserved urea recognition motif (URM) and the urea transport via H-bond transfer along the Q-T-T-Q motif among different UT members. Moreover, distinct binding modes of the competitive inhibitors 25a and ATB3, the uncompetitive inhibitor CF11 and the noncompetitive inhibitor HQA2 provide different mechanisms for blocking urea transport and achieved selectivity through L-P pocket, UCBP region and SCG pocket, respectively. In summary, our study not only allows structural understanding of urea transport via UTs but also afforded a structural landscape of hUT-A2 inhibition by competitive, uncompetitive and noncompetitive inhibitors, which may facilitate developing selective human UT-A inhibitors as a new class of salt-sparing diuretics.
リンク	Nat Commun / PubMed:39587082 / PubMed Central
手法	EM (単粒子)
解像度	2.3 - 3.3 Å
構造データ	38268 8xd7 EMDB-38268, PDB-8xd7: Cryo-EM structure of inhibitor 25a bound human urea transporter A2. 手法: EM (単粒子) / 解像度: 2.6 Å 38270 8xd9 EMDB-38270, PDB-8xd9: Cryo-EM structure of human urea transporter A2. 手法: EM (単粒子) / 解像度: 2.8 Å 38271 8xda EMDB-38271, PDB-8xda: Cryo-EM structure of urea bound human urea transporter A2. 手法: EM (単粒子) / 解像度: 3.0 Å 38272 8xdb EMDB-38272, PDB-8xdb: Cryo-EM structure of human urea transporter A2. 手法: EM (単粒子) / 解像度: 3.3 Å 38273 8xdc EMDB-38273, PDB-8xdc: Cryo-EM structure of human urea transporter A2. 手法: EM (単粒子) / 解像度: 3.0 Å 38274 8xdd EMDB-38274, PDB-8xdd: Cryo-EM structure of human urea transporter A2. 手法: EM (単粒子) / 解像度: 3.0 Å 38275 8xde EMDB-38275, PDB-8xde: Cryo-EM structure of human urea transporter A3. 手法: EM (単粒子) / 解像度: 2.3 Å 38276 8xdf EMDB-38276, PDB-8xdf: Cryo-EM structure of human urea transporter B. 手法: EM (単粒子) / 解像度: 2.4 Å 38277 8xdg EMDB-38277, PDB-8xdg: Cryo-EM structure of zebrafish urea transporter. 手法: EM (単粒子) / 解像度: 3.1 Å 38278 8xdh EMDB-38278, PDB-8xdh: Cryo-EM structure of zebrafish urea transporter. 手法: EM (単粒子) / 解像度: 3.1 Å 38279 8xdi EMDB-38279, PDB-8xdi: Cryo-EM structure of zebrafish urea transporter. 手法: EM (単粒子) / 解像度: 3.1 Å
化合物	PDB-1lu9: Structure of methylene-tetrahydromethanopterin dehydrogenase from Methylobacterium extorquens AM1 ChemComp-URE: UREA / 尿素 ChemComp-HOH: WATER PDB-1lyj: DISSECTION OF HELIX CAPPING IN T4 LYSOZYME BY STRUCTURAL AND THERMODYNAMIC ANALYSIS OF SIX AMINO ACID SUBSTITUTIONS AT THR 59 PDB-1lva: Crystal structure of a C-terminal fragment of Moorella thermoacetica elongation factor SelB ChemComp-8HC: 8-hydroxyquinoline-2-carboxylic acid / 8-ヒドロキシキノリン-2-カルボン酸 ChemComp-SZ4: 1-(3-methoxyphenyl)methanamine / 3-メトキシベンジルアミン
由来	homo sapiens (ヒト) homo sapien (ヒト) danio rerio (ゼブラフィッシュ)
キーワード	MEMBRANE PROTEIN / Urea transporter