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	Inhibition of M. tuberculosis and human ATP synthase by BDQ and TBAJ-587.
ジャーナル・号・ページ	Nature, Vol. 631, Issue 8020, Page 409-414, Year 2024
掲載日	2024年7月3日
著者	Yuying Zhang / Yuezheng Lai / Shan Zhou / Ting Ran / Yue Zhang / Ziqing Zhao / Ziyan Feng / Long Yu / Jinxu Xu / Kun Shi / Jianyun Wang / Yu Pang / Liang Li / Hongming Chen / Luke W Guddat / Yan Gao / Fengjiang Liu / Zihe Rao / Hongri Gong /
PubMed 要旨	Bedaquiline (BDQ), a first-in-class diarylquinoline anti-tuberculosis drug, and its analogue, TBAJ-587, prevent the growth and proliferation of Mycobacterium tuberculosis by inhibiting ATP synthase. ...Bedaquiline (BDQ), a first-in-class diarylquinoline anti-tuberculosis drug, and its analogue, TBAJ-587, prevent the growth and proliferation of Mycobacterium tuberculosis by inhibiting ATP synthase. However, BDQ also inhibits human ATP synthase. At present, how these compounds interact with either M. tuberculosis ATP synthase or human ATP synthase is unclear. Here we present cryogenic electron microscopy structures of M. tuberculosis ATP synthase with and without BDQ and TBAJ-587 bound, and human ATP synthase bound to BDQ. The two inhibitors interact with subunit a and the c-ring at the leading site, c-only sites and lagging site in M. tuberculosis ATP synthase, showing that BDQ and TBAJ-587 have similar modes of action. The quinolinyl and dimethylamino units of the compounds make extensive contacts with the protein. The structure of human ATP synthase in complex with BDQ reveals that the BDQ-binding site is similar to that observed for the leading site in M. tuberculosis ATP synthase, and that the quinolinyl unit also interacts extensively with the human enzyme. This study will improve researchers' understanding of the similarities and differences between human ATP synthase and M. tuberculosis ATP synthase in terms of the mode of BDQ binding, and will allow the rational design of novel diarylquinolines as anti-tuberculosis drugs.
リンク	Nature / PubMed:38961288
手法	EM (単粒子)
解像度	2.58 - 3.95 Å
構造データ	35909 8j0s EMDB-35909, PDB-8j0s: Cryo-EM structure of Mycobacterium tuberculosis ATP synthase in complex with bedaquiline(BDQ) 手法: EM (単粒子) / 解像度: 2.58 Å 35911 8j0t EMDB-35911, PDB-8j0t: Cryo-EM structure of Mycobacterium tuberculosis ATP synthase in the apo-form 手法: EM (単粒子) / 解像度: 2.8 Å 35982 8j57 EMDB-35982, PDB-8j57: Cryo-EM structure of Mycobacterium tuberculosis ATP synthase Fo in complex with bedaquiline(BDQ) 手法: EM (単粒子) / 解像度: 2.85 Å 35983 8j58 EMDB-35983, PDB-8j58: Cryo-EM structure of Mycobacterium tuberculosis ATP synthase Fo in the apo-form 手法: EM (単粒子) / 解像度: 3.15 Å EMDB-36015: Mycobacterium tuberculosis ATP synthase Peripheral Stalk in the apo-form 手法: EM (単粒子) / 解像度: 3.93 Å EMDB-36017: Mycobacterium tuberculosis ATP synthase Peripheral Stalk in complex with bedaquiline(BDQ) 手法: EM (単粒子) / 解像度: 3.89 Å EMDB-36028: Mycobacterium tuberculosis ATP synthase F1 in the apo-form 手法: EM (単粒子) / 解像度: 2.8 Å EMDB-36031: Mycobacterium tuberculosis ATP synthase F1 in complex with bedaquiline(BDQ) 手法: EM (単粒子) / 解像度: 2.58 Å 36589 8jr0 EMDB-36589, PDB-8jr0: Cryo-EM structure of Mycobacterium tuberculosis ATP synthase in complex with TBAJ-587 手法: EM (単粒子) / 解像度: 2.8 Å 36590 8jr1 EMDB-36590, PDB-8jr1: Cryo-EM structure of Mycobacterium tuberculosis ATP synthase Fo in complex with TBAJ-587 手法: EM (単粒子) / 解像度: 3.17 Å EMDB-36631: Cryo-EM structure of Mycobacterium tuberculosis ATP synthase F1 in complex with TBAJ-587 手法: EM (単粒子) / 解像度: 2.8 Å EMDB-36632: Cryo-EM structure of Mycobacterium tuberculosis ATP synthase Peripheral Stalk in complex with TBAJ-587 手法: EM (単粒子) / 解像度: 3.95 Å 37243 8khf EMDB-37243, PDB-8khf: Structure of the human ATP synthase bound to bedaquiline (membrane domain) 手法: EM (単粒子) / 解像度: 3.13 Å EMDB-37244: Structure of the human ATP synthase bound to bedaquiline 手法: EM (単粒子) / 解像度: 2.89 Å EMDB-37245: Structure of the human ATP synthase bound to bedaquiline (peripheral stalk domain) 手法: EM (単粒子) / 解像度: 3.77 Å 37251 8ki3 EMDB-37251, PDB-8ki3: Structure of the human ATP synthase bound to bedaquiline (composite) 手法: EM (単粒子) / 解像度: 2.89 Å
化合物	ChemComp-ATP: ADENOSINE-5'-TRIPHOSPHATE / ATP / ATP, エネルギー貯蔵分子YM ChemComp-MG: Unknown entry / マグネシウムジカチオン ChemComp-ADP: ADENOSINE-5'-DIPHOSPHATE / ADP / ADP, エネルギー貯蔵分子YM ChemComp-BQ1: Bedaquiline / ベダキリン / 薬剤, 抗生剤YM 化合物画像なし ChemComp-UTI*: Unknown entry
由来	mycobacterium tuberculosis (結核菌) homo sapiens (ヒト)
キーワード	MEMBRANE PROTEIN / ATP synthase / Mycobacterium tuberculosis / cryo-EM / Human