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	Inhibition of M. tuberculosis and human ATP synthase by BDQ and TBAJ-587.
Journal, issue, pages	Nature, Vol. 631, Issue 8020, Page 409-414, Year 2024
Publish date	Jul 3, 2024
Authors	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 Abstract	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.
External links	Nature / PubMed:38961288
Methods	EM (single particle)
Resolution	2.58 - 3.95 Å
Structure data	35909 8j0s EMDB-35909, PDB-8j0s: Cryo-EM structure of Mycobacterium tuberculosis ATP synthase in complex with bedaquiline(BDQ) Method: EM (single particle) / Resolution: 2.58 Å 35911 8j0t EMDB-35911, PDB-8j0t: Cryo-EM structure of Mycobacterium tuberculosis ATP synthase in the apo-form Method: EM (single particle) / Resolution: 2.8 Å 35982 8j57 EMDB-35982, PDB-8j57: Cryo-EM structure of Mycobacterium tuberculosis ATP synthase Fo in complex with bedaquiline(BDQ) Method: EM (single particle) / Resolution: 2.85 Å 35983 8j58 EMDB-35983, PDB-8j58: Cryo-EM structure of Mycobacterium tuberculosis ATP synthase Fo in the apo-form Method: EM (single particle) / Resolution: 3.15 Å EMDB-36015: Mycobacterium tuberculosis ATP synthase Peripheral Stalk in the apo-form Method: EM (single particle) / Resolution: 3.93 Å EMDB-36017: Mycobacterium tuberculosis ATP synthase Peripheral Stalk in complex with bedaquiline(BDQ) Method: EM (single particle) / Resolution: 3.89 Å EMDB-36028: Mycobacterium tuberculosis ATP synthase F1 in the apo-form Method: EM (single particle) / Resolution: 2.8 Å EMDB-36031: Mycobacterium tuberculosis ATP synthase F1 in complex with bedaquiline(BDQ) Method: EM (single particle) / Resolution: 2.58 Å 36589 8jr0 EMDB-36589, PDB-8jr0: Cryo-EM structure of Mycobacterium tuberculosis ATP synthase in complex with TBAJ-587 Method: EM (single particle) / Resolution: 2.8 Å 36590 8jr1 EMDB-36590, PDB-8jr1: Cryo-EM structure of Mycobacterium tuberculosis ATP synthase Fo in complex with TBAJ-587 Method: EM (single particle) / Resolution: 3.17 Å EMDB-36631: Cryo-EM structure of Mycobacterium tuberculosis ATP synthase F1 in complex with TBAJ-587 Method: EM (single particle) / Resolution: 2.8 Å EMDB-36632: Cryo-EM structure of Mycobacterium tuberculosis ATP synthase Peripheral Stalk in complex with TBAJ-587 Method: EM (single particle) / Resolution: 3.95 Å 37243 8khf EMDB-37243, PDB-8khf: Structure of the human ATP synthase bound to bedaquiline (membrane domain) Method: EM (single particle) / Resolution: 3.13 Å EMDB-37244: Structure of the human ATP synthase bound to bedaquiline Method: EM (single particle) / Resolution: 2.89 Å EMDB-37245: Structure of the human ATP synthase bound to bedaquiline (peripheral stalk domain) Method: EM (single particle) / Resolution: 3.77 Å 37251 8ki3 EMDB-37251, PDB-8ki3: Structure of the human ATP synthase bound to bedaquiline (composite) Method: EM (single particle) / Resolution: 2.89 Å
Chemicals	ChemComp-ATP: ADENOSINE-5'-TRIPHOSPHATE / ATP, energy-carrying moleculeYM ChemComp-MG: Unknown entry ChemComp-ADP: ADENOSINE-5'-DIPHOSPHATE / ADP, energy-carrying moleculeYM ChemComp-BQ1: Bedaquiline / medication, antibioticYM ChemComp, No image ChemComp-UTI*: Unknown entry
Source	mycobacterium tuberculosis (bacteria) homo sapiens (human)
Keywords	MEMBRANE PROTEIN / ATP synthase / Mycobacterium tuberculosis / cryo-EM / Human