7E1V

Cryo-EM structure of apo hybrid respiratory supercomplex consisting of Mycobacterium tuberculosis complexIII and Mycobacterium smegmatis complexIV

Summary for 7E1V

• Entry DOI: 10.2210/pdb7e1v/pdb
• EMDB information: 30943
• Descriptor: Cytochrome c oxidase subunit 2, Cytochrome bc1 complex cytochrome c subunit, COPPER (II) ION, ... (20 entities in total)
• Functional Keywords: mycobacterium smegmatis, mycobacterium tuberculosis, complexiii, complexiv, electron transport, anti-tb drugs, oxidoreductase
• Biological source: Mycobacterium tuberculosis H37Rv; More
• Total number of polymer chains: 20
• Total formula weight: 672680.63

Authors

Zhou, S.,Wang, W.,Gao, Y.,Gong, H.,Rao, Z. (deposition date: 2021-02-03, release date: 2021-10-13, Last modification date: 2024-11-06)

Primary citation

Zhou, S.,Wang, W.,Zhou, X.,Zhang, Y.,Lai, Y.,Tang, Y.,Xu, J.,Li, D.,Lin, J.,Yang, X.,Ran, T.,Chen, H.,Guddat, L.W.,Wang, Q.,Gao, Y.,Rao, Z.,Gong, H.
Structure of Mycobacterium tuberculosis cytochrome bcc in complex with Q203 and TB47, two anti-TB drug candidates.
Elife, 10:-, 2021

PubMed Abstract: Pathogenic mycobacteria pose a sustained threat to global human health. Recently, cytochrome complexes have gained interest as targets for antibiotic drug development. However, there is currently no structural information for the cytochrome complex from these pathogenic mycobacteria. Here, we report the structures of cytochrome alone (2.68 Å resolution) and in complex with clinical drug candidates Q203 (2.67 Å resolution) and TB47 (2.93 Å resolution) determined by single-particle cryo-electron microscopy. cytochrome forms a dimeric assembly with endogenous menaquinone/menaquinol bound at the quinone/quinol-binding pockets. We observe Q203 and TB47 bound at the quinol-binding site and stabilized by hydrogen bonds with the side chains of Thr and Glu, residues that are conserved across pathogenic mycobacteria. These high-resolution images provide a basis for the design of new mycobacterial cytochrome inhibitors that could be developed into broad-spectrum drugs to treat mycobacterial infections.

PubMed: 34819223
DOI: 10.7554/eLife.69418

Experimental method

ELECTRON MICROSCOPY (2.68 Å)