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	Mechanism of mycobacterial ATP synthase inhibition by squaramides and second generation diarylquinolines.
Journal, issue, pages	EMBO J, Vol. 42, Issue 15, Page e113687, Year 2023
Publish date	Aug 1, 2023
Authors	Gautier M Courbon / Paul R Palme / Lea Mann / Adrian Richter / Peter Imming / John L Rubinstein /
PubMed Abstract	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.
External links	EMBO J / PubMed:37377118 / PubMed Central
Methods	EM (single particle)
Resolution	2.6 - 3.1 Å
Structure data	29648 8g07 EMDB-29648, PDB-8g07: Cryo-EM structure of SQ31f-bound Mycobacterium smegmatis ATP synthase FO region Method: EM (single particle) / Resolution: 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) Method: EM (single particle) / Resolution: 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) Method: EM (single particle) / Resolution: 3.1 Å 29651 8g0a EMDB-29651, PDB-8g0a: Cryo-EM structure of SQ31f-bound Mycobacterium smegmatis ATP synthase rotational state 3 Method: EM (single particle) / Resolution: 2.9 Å 29652 8g0b EMDB-29652, PDB-8g0b: Cryo-EM structure of TBAJ-876-bound Mycobacterium smegmatis ATP synthase FO region Method: EM (single particle) / Resolution: 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) Method: EM (single particle) / Resolution: 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) Method: EM (single particle) / Resolution: 2.9 Å 29655 8g0e EMDB-29655, PDB-8g0e: Cryo-EM structure of TBAJ-876-bound Mycobacterium smegmatis ATP synthase rotational state 3 Method: EM (single particle) / Resolution: 2.6 Å
Chemicals	ChemComp-SQC: 3-[4-(morpholin-4-yl)phenyl]-4-{[(pyridin-2-yl)methyl]amino}cyclobut-3-ene-1,2-dione ChemComp-ATP: ADENOSINE-5'-TRIPHOSPHATE / ATP, energy-carrying moleculeYM ChemComp-MG: Unknown entry ChemComp-PO4: PHOSPHATE ION 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
Source	mycolicibacterium smegmatis mc2 155 (bacteria)
Keywords	TRANSLOCASE/INHIBITOR / ATP synthase / mycobacterial / inhibitor / tuberculosis / antibiotic / HYDROLASE / TRANSLOCASE-INHIBITOR complex