Structure of Mycobacterium tuberculosis cytochrome bcc in complex with Q203 and TB47, two anti-TB drug candidates
| Autor: | Luke W. Guddat, Quan Wang, Shan Zhou, Jianping Lin, Hongri Gong, Yuying Zhang, Jinxu Xu, Weiwei Wang, Xiaolin Yang, Ting Ran, Yuezheng Lai, Hongming Chen, Dongmei Li, Yanting Tang, Zihe Rao, Xiaoting Zhou, Yan Gao |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Antibiotic drug
Drug Tuberculosis Cytochrome TB47 QH301-705.5 media_common.quotation_subject Science cryo-electron microscopy General Biochemistry Genetics and Molecular Biology Microbiology Mycobacterium tuberculosis Human health medicine Biology (General) media_common General Immunology and Microbiology biology Chemistry General Neuroscience General Medicine medicine.disease biology.organism_classification Structural biology biology.protein Medicine cytochrome bcc complex Q203 |
| Zdroj: | eLife, Vol 10 (2021) |
| Popis: | Pathogenic mycobacteria pose a sustained threat to global human health. Recently, cytochrome bcc complexes have gained interest as targets for antibiotic drug development. However, there is currently no structural information for the cytochrome bcc complex from these pathogenic mycobacteria. Here, we report the structures of Mycobacterium tuberculosis cytochrome bcc 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. M. tuberculosis cytochrome bcc 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 QcrBThr313 and QcrBGlu314, residues that are conserved across pathogenic mycobacteria. These high-resolution images provide a basis for the design of new mycobacterial cytochrome bcc inhibitors that could be developed into broad-spectrum drugs to treat mycobacterial infections. |
| Databáze: | OpenAIRE |
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