Database of articles cited by EMDB/PDB/SASBDB data

Keywords
Structure methods	All X-ray diffraction NMR electron microscopy small angle scattering neutron diffraction fiber diffraction powder diffraction infrared spectroscopy EPR fluorescence transfer theoretical model Hybrid
Author
Journal
IF	>30 >20 >10 >5 all

Title	Structure of mycobacterial ATP synthase bound to the tuberculosis drug bedaquiline.
Journal, issue, pages	Nature, Vol. 589, Issue 7840, Page 143-147, Year 2021
Publish date	Dec 9, 2020
Authors	Hui Guo / Gautier M Courbon / Stephanie A Bueler / Juntao Mai / Jun Liu / John L Rubinstein /
PubMed Abstract	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.
External links	Nature / PubMed:33299175
Methods	EM (single particle)
Resolution	3.2 - 3.7 Å
Structure data	22311 7jg5 EMDB-22311, PDB-7jg5: Cryo-EM structure of bedaquiline-free Mycobacterium smegmatis ATP synthase rotational state 1 Method: EM (single particle) / Resolution: 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) Method: EM (single particle) / Resolution: 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) Method: EM (single particle) / Resolution: 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) Method: EM (single particle) / Resolution: 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) Method: EM (single particle) / Resolution: 3.4 Å 22316 7jga EMDB-22316, PDB-7jga: Cryo-EM structure of bedaquiline-saturated Mycobacterium smegmatis ATP synthase rotational state 3 Method: EM (single particle) / Resolution: 3.2 Å EMDB-22317: Cryo-EM structure of bedaquiline-washed Mycobacterium smegmatis ATP synthase rotational state 1 Method: EM (single particle) / Resolution: 3.3 Å EMDB-22318: Cryo-EM structure of bedaquiline-washed Mycobacterium smegmatis ATP synthase rotational state 2 Method: EM (single particle) / Resolution: 3.5 Å EMDB-22319: Cryo-EM structure of bedaquiline-washed Mycobacterium smegmatis ATP synthase rotational state 3 Method: EM (single particle) / Resolution: 3.3 Å 22320 7jgb EMDB-22320, PDB-7jgb: Cryo-EM structure of bedaquiline-free Mycobacterium smegmatis ATP synthase FO region Method: EM (single particle) / Resolution: 3.5 Å 22321 7jgc EMDB-22321, PDB-7jgc: Cryo-EM structure of bedaquiline-saturated Mycobacterium smegmatis ATP synthase FO region Method: EM (single particle) / Resolution: 3.4 Å EMDB-22322: Cryo-EM structure of bedaquiline-washed Mycobacterium smegmatis ATP synthase FO region Method: EM (single particle) / Resolution: 3.7 Å
Chemicals	ChemComp-ATP: ADENOSINE-5'-TRIPHOSPHATE / ATP, energy-carrying moleculeYM / Adenosine triphosphate ChemComp-MG: Unknown entry ChemComp-PO4: PHOSPHATE ION / Phosphate ChemComp-ADP: ADENOSINE-5'-DIPHOSPHATE / ADP, energy-carrying moleculeYM / Adenosine diphosphate ChemComp-BQ1: Bedaquiline / medication, antibiotic*YM / Bedaquiline
Source	mycolicibacterium smegmatis (bacteria)
Keywords	TRANSLOCASE / Bedaquiline / Sirturo / TMC207 / T207910 / ATP synthase / mycobacteria / tuberculosis / HYDROLASE