TY  - JOUR
A1  - Safarian, Schara
A1  - Opel-Reading, Helen K.
A1  - Wu, Di
A1  - Mehdipour, Ahmad Reza
A1  - Hards, Kiel
A1  - Harold, Liam K.
A1  - Radloff, Melanie
A1  - Stewart, Ian
A1  - Welsch, Sonja
A1  - Hummer, Gerhard
A1  - Cook, Gregory M.
A1  - Krause, Kurt L.
A1  - Michel, Hartmut
T1  - The cryo-EM structure of the bd oxidase from M. tuberculosis reveals a unique structural framework and enables rational drug design to combat TB
T2  - Nature Communications
N2  - 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.
KW  - Bacterial structural biology
KW  - Bioenergetics
KW  - Cryoelectron microscopy
KW  - Structural biology
Y1  - 2021
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/63252
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-632525
SN  - 2041-1723
N1  - Open Access funding enabled and organized by Projekt DEAL.
N1  - This work was supported by the Max Planck Society, the Nobel laureate Fellowship of the Max Planck Society, and the Deutsche Forschungsgemeinschaft (Cluster of Excellence Macromolecular Complexes Frankfurt), Marsden Fund, Anderson Charitable Trusts, Catalyst Fund, and Royal Society of New Zealand.
VL  - 12
IS  - art. 5236
SP  - 1
EP  - 10
PB  - Nature Publishing Group UK
CY  - [London]
ER  -