7NKZ

Cryo-EM structure of the cytochrome bd oxidase from M. tuberculosis at 2.5 A resolution

Summary for 7NKZ

• Entry DOI: 10.2210/pdb7nkz/pdb
• EMDB information: 12451
• Descriptor: Probable integral membrane cytochrome D ubiquinol oxidase (Subunit II) CydB (Cytochrome BD-I oxidase subunit II), Probable integral membrane cytochrome D ubiquinol oxidase (Subunit I) CydA (Cytochrome BD-I oxidase subunit I), OXYGEN MOLECULE, ... (7 entities in total)
• Functional Keywords: terminal oxidase oxidoreductase oxygen reductase bd oxidase, membrane protein
• Biological source: Mycobacterium tuberculosis H37Rv; More
• Total number of polymer chains: 2
• Total formula weight: 94200.78

Authors

Safarian, S.,Wu, D.,Krause, K.L.,Michel, H. (deposition date: 2021-02-19, release date: 2021-09-22, Last modification date: 2024-10-23)

Primary citation

Safarian, S.,Opel-Reading, H.K.,Wu, D.,Mehdipour, A.R.,Hards, K.,Harold, L.K.,Radloff, M.,Stewart, I.,Welsch, S.,Hummer, G.,Cook, G.M.,Krause, K.L.,Michel, H.
The cryo-EM structure of the bd oxidase from M. tuberculosis reveals a unique structural framework and enables rational drug design to combat TB.
Nat Commun, 12:5236-5236, 2021

PubMed Abstract: New drugs are urgently needed to combat the global TB epidemic. Targeting simultaneously multiple respiratory enzyme complexes of Mycobacterium tuberculosis is regarded as one of the most effective treatment options to shorten drug administration regimes, and reduce the opportunity for the emergence of drug resistance. During infection and proliferation, the cytochrome bd oxidase plays a crucial role for mycobacterial pathophysiology by maintaining aerobic respiration at limited oxygen concentrations. Here, we present the cryo-EM structure of the cytochrome bd oxidase from M. tuberculosis at 2.5 Å. In conjunction with atomistic molecular dynamics (MD) simulation studies we discovered a previously unknown MK-9-binding site, as well as a unique disulfide bond within the Q-loop domain that defines an inactive conformation of the canonical quinol oxidation site in Actinobacteria. Our detailed insights into the long-sought atomic framework of the cytochrome bd oxidase from M. tuberculosis will form the basis for the design of highly specific drugs to act on this enzyme.

PubMed: 34475399
DOI: 10.1038/s41467-021-25537-z

Experimental method

ELECTRON MICROSCOPY (2.5 Å)