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	Mechanism of mycobacterial ATP synthase inhibition by squaramides and second generation diarylquinolines.
ジャーナル・号・ページ	EMBO J, Vol. 42, Issue 15, Page e113687, Year 2023
掲載日	2023年8月1日
著者	Gautier M Courbon / Paul R Palme / Lea Mann / Adrian Richter / Peter Imming / John L Rubinstein /
PubMed 要旨	Mycobacteria, such as Mycobacterium tuberculosis, depend on the activity of adenosine triphosphate (ATP) synthase for growth. The diarylquinoline bedaquiline (BDQ), a mycobacterial ATP synthase ...Mycobacteria, such as Mycobacterium tuberculosis, depend on the activity of adenosine triphosphate (ATP) synthase for growth. The diarylquinoline bedaquiline (BDQ), a mycobacterial ATP synthase inhibitor, is an important medication for treatment of drug-resistant tuberculosis but suffers from off-target effects and is susceptible to resistance mutations. Consequently, both new and improved mycobacterial ATP synthase inhibitors are needed. We used electron cryomicroscopy and biochemical assays to study the interaction of Mycobacterium smegmatis ATP synthase with the second generation diarylquinoline TBAJ-876 and the squaramide inhibitor SQ31f. The aryl groups of TBAJ-876 improve binding compared with BDQ, while SQ31f, which blocks ATP synthesis ~10 times more potently than ATP hydrolysis, binds a previously unknown site in the enzyme's proton-conducting channel. Remarkably, BDQ, TBAJ-876, and SQ31f all induce similar conformational changes in ATP synthase, suggesting that the resulting conformation is particularly suited for drug binding. Further, high concentrations of the diarylquinolines uncouple the transmembrane proton motive force while for SQ31f they do not, which may explain why high concentrations of diarylquinolines, but not SQ31f, have been reported to kill mycobacteria.
リンク	EMBO J / PubMed:37377118 / PubMed Central
手法	EM (単粒子)
解像度	2.6 - 3.1 Å
構造データ	29648 8g07 EMDB-29648, PDB-8g07: Cryo-EM structure of SQ31f-bound Mycobacterium smegmatis ATP synthase FO region 手法: EM (単粒子) / 解像度: 2.8 Å 29649 8g08 EMDB-29649: Cryo-EM structure of SQ31f-bound Mycobacterium smegmatis ATP synthase rotational state 1 PDB-8g08: Cryo-EM structure of SQ31f-bound Mycobacterium smegmatis ATP synthase rotational state 1 (backbone model) 手法: EM (単粒子) / 解像度: 2.8 Å 29650 8g09 EMDB-29650: Cryo-EM structure of SQ31f-bound Mycobacterium smegmatis ATP synthase rotational state 2 PDB-8g09: Cryo-EM structure of SQ31f-bound Mycobacterium smegmatis ATP synthase rotational state 2 (backbone model) 手法: EM (単粒子) / 解像度: 3.1 Å 29651 8g0a EMDB-29651, PDB-8g0a: Cryo-EM structure of SQ31f-bound Mycobacterium smegmatis ATP synthase rotational state 3 手法: EM (単粒子) / 解像度: 2.9 Å 29652 8g0b EMDB-29652, PDB-8g0b: Cryo-EM structure of TBAJ-876-bound Mycobacterium smegmatis ATP synthase FO region 手法: EM (単粒子) / 解像度: 2.8 Å 29653 8g0c EMDB-29653: Cryo-EM structure of TBAJ-876-bound Mycobacterium smegmatis ATP synthase rotational state 1 PDB-8g0c: Cryo-EM structure of TBAJ-876-bound Mycobacterium smegmatis ATP synthase rotational state 1 (backbone model) 手法: EM (単粒子) / 解像度: 2.8 Å 29654 8g0d EMDB-29654: Cryo-EM structure of TBAJ-876-bound Mycobacterium smegmatis ATP synthase rotational state 2 PDB-8g0d: Cryo-EM structure of TBAJ-876-bound Mycobacterium smegmatis ATP synthase rotational state 2 (backbone model) 手法: EM (単粒子) / 解像度: 2.9 Å 29655 8g0e EMDB-29655, PDB-8g0e: Cryo-EM structure of TBAJ-876-bound Mycobacterium smegmatis ATP synthase rotational state 3 手法: EM (単粒子) / 解像度: 2.6 Å
化合物	ChemComp-SQC: 3-[4-(morpholin-4-yl)phenyl]-4-{[(pyridin-2-yl)methyl]amino}cyclobut-3-ene-1,2-dione / 3-(4-モルホリノフェニル)-4-(2-ピリジニルメチルアミノ)-3-シクロブテン-1,2-ジオン 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-PO4: PHOSPHATE ION / ホスファ-ト ChemComp-YGR*: (1R,2S)-1-(6-bromo-2-methoxyquinolin-3-yl)-2-(2,6-dimethoxypyridin-4-yl)-4-(dimethylamino)-1-(2,3,6-trimethoxypyridin-4-yl)butan-2-ol
由来	mycolicibacterium smegmatis mc2 155 (バクテリア)
キーワード	TRANSLOCASE/INHIBITOR / ATP synthase / mycobacterial / inhibitor / tuberculosis / antibiotic / HYDROLASE / TRANSLOCASE-INHIBITOR complex