7jgc

Cryo-EM structure of bedaquiline-saturated Mycobacterium smegmatis ATP synthase FO region

spinqualitylabelsall models 7jgc, resolution 3.40Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7jgc is a 12 chain structure with sequence from Mycolicibacterium smegmatis. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 3.4Å Ligands: BQ1 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function A0R206_MYCS2 Key component of the proton channel; it plays a direct role in the translocation of protons across the membrane.[HAMAP-Rule:MF_01393][RuleBase:RU000483] Publication Abstract from PubMed Tuberculosis-the world's leading cause of death by infectious disease-is increasingly resistant to current first-line antibiotics(1). The bacterium Mycobacterium tuberculosis (which causes tuberculosis) can survive low-energy conditions, allowing infections to remain dormant and decreasing their susceptibility to many antibiotics(2). Bedaquiline was developed in 2005 from a lead compound identified in a phenotypic screen against Mycobacterium smegmatis(3). This drug can sterilize even latent M. tuberculosis infections(4) and has become a cornerstone of treatment for multidrug-resistant and extensively drug-resistant tuberculosis(1,5,6). Bedaquiline targets the mycobacterial ATP synthase(3), which is an essential enzyme in the obligate aerobic Mycobacterium genus(3,7), 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 alpha-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. Structure of mycobacterial ATP synthase bound to the tuberculosis drug bedaquiline.,Guo H, Courbon GM, Bueler SA, Mai J, Liu J, Rubinstein JL Nature. 2021 Jan;589(7840):143-147. doi: 10.1038/s41586-020-3004-3. Epub 2020 Dec , 9. PMID:33299175 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also ATPase 3D structures

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