Schara Safarian, Helen K. Opel-Reading, Di Wu, Ahmad Reza Mehdipour, Kiel Hards, Liam K. Harold, Melanie Radloff, Ian Stewart, Sonja Welsch, Gerhard Hummer, Gregory M. Cook, Kurt L. Krause, Hartmut Michel
- 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.
MetadatenAuthor: | Schara SafarianORCiDGND, Helen K. Opel-Reading, Di WuORCiDGND, Ahmad Reza MehdipourORCiDGND, Kiel Hards, Liam K. Harold, Melanie Radloff, Ian Stewart, Sonja WelschORCiDGND, Gerhard HummerORCiD, Gregory M. Cook, Kurt L. Krause, Hartmut MichelORCiDGND |
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URN: | urn:nbn:de:hebis:30:3-632525 |
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DOI: | https://doi.org/10.1038/s41467-021-25537-z |
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ISSN: | 2041-1723 |
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Parent Title (English): | Nature Communications |
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Publisher: | Nature Publishing Group UK |
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Place of publication: | [London] |
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Document Type: | Article |
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Language: | English |
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Date of Publication (online): | 2021/09/02 |
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Date of first Publication: | 2021/09/02 |
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Publishing Institution: | Universitätsbibliothek Johann Christian Senckenberg |
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Release Date: | 2022/02/16 |
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Tag: | Bacterial structural biology; Bioenergetics; Cryoelectron microscopy; Structural biology |
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Volume: | 12 |
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Issue: | art. 5236 |
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Page Number: | 10 |
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First Page: | 1 |
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Last Page: | 10 |
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Note: | Open Access funding enabled and organized by Projekt DEAL. |
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Note: | 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. |
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HeBIS-PPN: | 491746369 |
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Institutes: | Physik |
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Dewey Decimal Classification: | 5 Naturwissenschaften und Mathematik / 53 Physik / 530 Physik |
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| 5 Naturwissenschaften und Mathematik / 54 Chemie / 540 Chemie und zugeordnete Wissenschaften |
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| 5 Naturwissenschaften und Mathematik / 57 Biowissenschaften; Biologie / 570 Biowissenschaften; Biologie |
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| 6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit |
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Sammlungen: | Universitätspublikationen |
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Licence (German): | Creative Commons - Namensnennung 4.0 |
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