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	Structure of mycobacterial ATP synthase bound to the tuberculosis drug bedaquiline.
ジャーナル・号・ページ	Nature, Vol. 589, Issue 7840, Page 143-147, Year 2021
掲載日	2020年12月9日
著者	Hui Guo / Gautier M Courbon / Stephanie A Bueler / Juntao Mai / Jun Liu / John L Rubinstein /
PubMed 要旨	Tuberculosis-the world's leading cause of death by infectious disease-is increasingly resistant to current first-line antibiotics. The bacterium Mycobacterium tuberculosis (which causes tuberculosis) ...Tuberculosis-the world's leading cause of death by infectious disease-is increasingly resistant to current first-line antibiotics. The bacterium Mycobacterium tuberculosis (which causes tuberculosis) can survive low-energy conditions, allowing infections to remain dormant and decreasing their susceptibility to many antibiotics. Bedaquiline was developed in 2005 from a lead compound identified in a phenotypic screen against Mycobacterium smegmatis. This drug can sterilize even latent M. tuberculosis infections and has become a cornerstone of treatment for multidrug-resistant and extensively drug-resistant tuberculosis. Bedaquiline targets the mycobacterial ATP synthase, which is an essential enzyme in the obligate aerobic Mycobacterium genus, but how it binds the intact enzyme is unknown. Here we determined cryo-electron microscopy structures of M. smegmatis ATP synthase alone and in complex with bedaquiline. The drug-free structure suggests that hook-like extensions from the α-subunits prevent the enzyme from running in reverse, inhibiting ATP hydrolysis and preserving energy in hypoxic conditions. Bedaquiline binding induces large conformational changes in the ATP synthase, creating tight binding pockets at the interface of subunits a and c that explain the potency of this drug as an antibiotic for tuberculosis.
リンク	Nature / PubMed:33299175
手法	EM (単粒子)
解像度	3.2 - 3.7 Å
構造データ	22311 7jg5 EMDB-22311, PDB-7jg5: Cryo-EM structure of bedaquiline-free Mycobacterium smegmatis ATP synthase rotational state 1 手法: EM (単粒子) / 解像度: 3.4 Å 22312 7jg6 EMDB-22312: Cryo-EM structure of bedaquiline-free Mycobacterium smegmatis ATP synthase rotational state 2 PDB-7jg6: Cryo-EM structure of bedaquiline-free Mycobacterium smegmatis ATP synthase rotational state 2 (backbone model) 手法: EM (単粒子) / 解像度: 3.7 Å 22313 7jg7 EMDB-22313: Cryo-EM structure of bedaquiline-free Mycobacterium smegmatis ATP synthase rotational state 3 PDB-7jg7: Cryo-EM structure of bedaquiline-free Mycobacterium smegmatis ATP synthase rotational state 3 (backbone model) 手法: EM (単粒子) / 解像度: 3.5 Å 22314 7jg8 EMDB-22314: Cryo-EM structure of bedaquiline-saturated Mycobacterium smegmatis ATP synthase rotational state 1 PDB-7jg8: Cryo-EM structure of bedaquiline-saturated Mycobacterium smegmatis ATP synthase rotational state 1 (backbone model) 手法: EM (単粒子) / 解像度: 3.3 Å 22315 7jg9 EMDB-22315: Cryo-EM structure of bedaquiline-saturated Mycobacterium smegmatis ATP synthase rotational state 2 PDB-7jg9: Cryo-EM structure of bedaquiline-saturated mycobacterium smegmatis ATP synthase rotational state 2 (backbone model) 手法: EM (単粒子) / 解像度: 3.4 Å 22316 7jga EMDB-22316, PDB-7jga: Cryo-EM structure of bedaquiline-saturated Mycobacterium smegmatis ATP synthase rotational state 3 手法: EM (単粒子) / 解像度: 3.2 Å EMDB-22317: Cryo-EM structure of bedaquiline-washed Mycobacterium smegmatis ATP synthase rotational state 1 手法: EM (単粒子) / 解像度: 3.3 Å EMDB-22318: Cryo-EM structure of bedaquiline-washed Mycobacterium smegmatis ATP synthase rotational state 2 手法: EM (単粒子) / 解像度: 3.5 Å EMDB-22319: Cryo-EM structure of bedaquiline-washed Mycobacterium smegmatis ATP synthase rotational state 3 手法: EM (単粒子) / 解像度: 3.3 Å 22320 7jgb EMDB-22320, PDB-7jgb: Cryo-EM structure of bedaquiline-free Mycobacterium smegmatis ATP synthase FO region 手法: EM (単粒子) / 解像度: 3.5 Å 22321 7jgc EMDB-22321, PDB-7jgc: Cryo-EM structure of bedaquiline-saturated Mycobacterium smegmatis ATP synthase FO region 手法: EM (単粒子) / 解像度: 3.4 Å EMDB-22322: Cryo-EM structure of bedaquiline-washed Mycobacterium smegmatis ATP synthase FO region 手法: EM (単粒子) / 解像度: 3.7 Å
化合物	ChemComp-ATP: ADENOSINE-5'-TRIPHOSPHATE / ATP / ATP, エネルギー貯蔵分子YM / アデノシン三リン酸 ChemComp-MG: Unknown entry / マグネシウムジカチオン ChemComp-PO4: PHOSPHATE ION / ホスファ-ト / リン酸塩 ChemComp-ADP: ADENOSINE-5'-DIPHOSPHATE / ADP / ADP, エネルギー貯蔵分子YM / アデノシン二リン酸 ChemComp-BQ1: Bedaquiline / ベダキリン / 薬剤, 抗生剤*YM / ベダキリン
由来	mycolicibacterium smegmatis (バクテリア)
キーワード	TRANSLOCASE (輸送酵素) / Bedaquiline (ベダキリン) / Sirturo (ベダキリン) / TMC207 (ベダキリン) / T207910 / ATP synthase (ATP合成酵素) / mycobacteria (マイコバクテリウム属) / tuberculosis (結核) / HYDROLASE (加水分解酵素)