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	Antiviral drug recognition and elevator-type transport motions of CNT3.
ジャーナル・号・ページ	Nat Chem Biol, Year 2024
掲載日	2024年2月28日
著者	Nicholas J Wright / Feng Zhang / Yang Suo / Lingyang Kong / Ying Yin / Justin G Fedor / Kedar Sharma / Mario J Borgnia / Wonpil Im / Seok-Yong Lee /
PubMed 要旨	Nucleoside analogs have broad clinical utility as antiviral drugs. Key to their systemic distribution and cellular entry are human nucleoside transporters. Here, we establish that the human ...Nucleoside analogs have broad clinical utility as antiviral drugs. Key to their systemic distribution and cellular entry are human nucleoside transporters. Here, we establish that the human concentrative nucleoside transporter 3 (CNT3) interacts with antiviral drugs used in the treatment of coronavirus infections. We report high-resolution single-particle cryo-electron microscopy structures of bovine CNT3 complexed with antiviral nucleosides N-hydroxycytidine, PSI-6206, GS-441524 and ribavirin, all in inward-facing states. Notably, we found that the orally bioavailable antiviral molnupiravir arrests CNT3 in four distinct conformations, allowing us to capture cryo-electron microscopy structures of drug-loaded outward-facing and drug-loaded intermediate states. Our studies uncover the conformational trajectory of CNT3 during membrane transport of a nucleoside analog antiviral drug, yield new insights into the role of interactions between the transport and the scaffold domains in elevator-like domain movements during drug translocation, and provide insights into the design of nucleoside analog antiviral prodrugs with improved oral bioavailability.
リンク	Nat Chem Biol / PubMed:38418906
手法	EM (単粒子)
解像度	2.31 - 6.92 Å
構造データ	41730 8tz1 EMDB-41730, PDB-8tz1: Cryo-EM structure of bovine concentrative nucleoside transporter 3 in complex with Ribavirin 手法: EM (単粒子) / 解像度: 2.54 Å 41731 8tz2 EMDB-41731, PDB-8tz2: Cryo-EM structure of bovine concentrative nucleoside transporter 3 in MSP2N2 nanodiscs, apo state 手法: EM (単粒子) / 解像度: 2.8 Å 41732 8tz3 EMDB-41732, PDB-8tz3: Cryo-EM structure of bovine concentrative nucleoside transporter 3 in complex with GS-441524, consensus reconstruction 手法: EM (単粒子) / 解像度: 2.31 Å 41733 8tz4 EMDB-41733, PDB-8tz4: Cryo-EM structure of bovine concentrative nucleoside transporter 3 in complex with GS-441524, subset reconstruction 手法: EM (単粒子) / 解像度: 3.23 Å 41734 8tz5 EMDB-41734, PDB-8tz5: Cryo-EM structure of bovine concentrative nucleoside transporter 3 in complex with N-hydroxycytidine 手法: EM (単粒子) / 解像度: 2.74 Å 41735 8tz6 EMDB-41735, PDB-8tz6: Cryo-EM structure of bovine concentrative nucleoside transporter 3 in complex with PSI-6206 手法: EM (単粒子) / 解像度: 2.69 Å 41736 8tz7 EMDB-41736, PDB-8tz7: Cryo-EM structure of bovine concentrative nucleoside transporter 3 in complex with Molnupiravir, condition 1, INT1-INT1-INT1 conformation 手法: EM (単粒子) / 解像度: 3.0 Å 41737 8tz8 EMDB-41737, PDB-8tz8: Cryo-EM structure of bovine concentrative nucleoside transporter 3 in complex with Molnupiravir, condition 1, INT1-INT1-INT3 conformation 手法: EM (単粒子) / 解像度: 3.19 Å 41738 8tz9 EMDB-41738, PDB-8tz9: Cryo-EM structure of bovine concentrative nucleoside transporter 3 in complex with Molnupiravir, condition 2, INT2-INT2-INT2 conformation 手法: EM (単粒子) / 解像度: 3.67 Å 41739 8tza EMDB-41739, PDB-8tza: Cryo-EM structure of bovine concentrative nucleoside transporter 3 in complex with Molnupiravir, condition 2, INT2-INT1-INT1 conformation 手法: EM (単粒子) / 解像度: 3.43 Å EMDB-41740: Cryo-EM reconstruction of bovine concentrative nucleoside transporter 3 in complex with Molnupiravir, condition 1, consensus reconstruction 手法: EM (単粒子) / 解像度: 2.8 Å EMDB-41741: Cryo-EM reconstruction of bovine concentrative nucleoside transporter 3 in complex with Molnupiravir, condition 1, OFS-OFS-OFS conformation 手法: EM (単粒子) / 解像度: 6.92 Å EMDB-41742: Cryo-EM reconstruction of bovine concentrative nucleoside transporter 3 in complex with Molnupiravir, condition 1, OFS-OFS-INT1 conformation 手法: EM (単粒子) / 解像度: 4.16 Å EMDB-41743: Cryo-EM reconstruction of bovine concentrative nucleoside transporter 3 in complex with Molnupiravir, condition 1, OFS-OFS-INT3 conformation 手法: EM (単粒子) / 解像度: 5.72 Å EMDB-41744: Cryo-EM reconstruction of bovine concentrative nucleoside transporter 3 in complex with Molnupiravir, condition 1, INT1-INT1-OFS conformation (from ensemble analysis) 手法: EM (単粒子) / 解像度: 3.4 Å EMDB-41745: Cryo-EM reconstruction of bovine concentrative nucleoside transporter 3 in complex with Molnupiravir, condition 1, INT3-INT3-OFS conformation 手法: EM (単粒子) / 解像度: 4.28 Å EMDB-41746: Cryo-EM reconstruction of bovine concentrative nucleoside transporter 3 in complex with Molnupiravir, condition 1, INT3-INT3-INT1 conformation 手法: EM (単粒子) / 解像度: 3.47 Å EMDB-41747: Cryo-EM reconstruction of bovine concentrative nucleoside transporter 3 in complex with Molnupiravir, condition 1, INT3-INT3-INT3 conformation 手法: EM (単粒子) / 解像度: 4.3 Å EMDB-41748: Cryo-EM reconstruction of bovine concentrative nucleoside transporter 3 in complex with Molnupiravir, condition 1, OFS-INT1-INT3 (clockwise) conformation 手法: EM (単粒子) / 解像度: 3.87 Å EMDB-41749: Cryo-EM reconstruction of bovine concentrative nucleoside transporter 3 in complex with Molnupiravir, condition 1, OFS-INT1-INT3 (counterclockwise) conformation 手法: EM (単粒子) / 解像度: 3.68 Å EMDB-41750: Cryo-EM reconstruction of bovine concentrative nucleoside transporter 3 in complex with Molnupiravir, condition 2, INT2-INT2-INT1 conformation 手法: EM (単粒子) / 解像度: 3.49 Å EMDB-41751: Cryo-EM reconstruction of bovine concentrative nucleoside transporter 3 in complex with Molnupiravir, condition 2, INT1-INT1-INT1 conformation 手法: EM (単粒子) / 解像度: 3.45 Å EMDB-41752: Cryo-EM reconstruction of bovine concentrative nucleoside transporter 3 in complex with Molnupiravir, condition 2, consensus reconstruction 手法: EM (単粒子) / 解像度: 2.99 Å 41755 8tzd EMDB-41755, PDB-8tzd: Cryo-EM structure of bovine concentrative nucleoside transporter 3 in complex with Molnupiravir, condition 1, INT1-INT1-OFS conformation (3DVA analysis) 手法: EM (単粒子) / 解像度: 3.2 Å
化合物	ChemComp-RBV: 1-(beta-D-ribofuranosyl)-1H-1,2,4-triazole-3-carboxamide / リバビリン / 薬剤, 抗ウイルス剤YM / リバビリン ChemComp-NA: Unknown entry / ナトリウムカチオン ChemComp-LBN: 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine / リン脂質YM / POホスファチジルコリン ChemComp-HOH: WATER / 水 ChemComp-U08: (2~{R},3~{R},4~{S},5~{R})-2-(4-azanylpyrrolo[2,1-f][1,2,4]triazin-7-yl)-5-(hydroxymethyl)-3,4-bis(oxidanyl)oxolane-2-carbonitrile / 抗ウイルス剤YM / GS-441524 化合物画像なし ChemComp-U56: Unknown entry 化合物画像なし ChemComp-U7I: Unknown entry 化合物画像なし ChemComp-XMO*: Unknown entry
由来	bos taurus (ウシ)
キーワード	TRANSPORT PROTEIN (運搬体タンパク質) / membrane protein (膜タンパク質) / transporter (運搬体タンパク質) / nucleoside (ヌクレオシド)