2. Academic Validation
  3. Structure of Mycobacterium tuberculosis cytochrome bcc in complex with Q203 and TB47, two anti-TB drug candidates

Structure of Mycobacterium tuberculosis cytochrome bcc in complex with Q203 and TB47, two anti-TB drug candidates

  • Elife. 2021 Nov 25;10:e69418. doi: 10.7554/eLife.69418.
Shan Zhou  # 1 2,  Weiwei Wang  # 3,  Xiaoting Zhou 3,  Yuying Zhang 2,  Yuezheng Lai 2,  Yanting Tang 2,  Jinxu Xu 2,  Dongmei Li 1,  Jianping Lin 1,  Xiaolin Yang 3,  Ting Ran 4,  Hongming Chen 4,  Luke W Guddat 5,  Quan Wang 3,  Yan Gao 3,  Zihe Rao 1 2 3 6 7,  Hongri Gong 2
Affiliations

Affiliations

  • 1 State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy, Nankai University, Tianjin, China.
  • 2 State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University, Tianjin, China.
  • 3 Shanghai Institute for Advanced Immunochemical Studies and School of Life Science and Technology, ShanghaiTech University, Shanghai, China.
  • 4 Bioland Laboratory (Guangzhou Regenerative Medicine and Health - Guangdong Laboratory), Guangzhou, China.
  • 5 School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, Australia.
  • 6 National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Beijing, China.
  • 7 Laboratory of Structural Biology, Tsinghua University, Beijing, China.
  • # Contributed equally.
PMID: 34819223 DOI: 10.7554/eLife.69418
Abstract

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.

Keywords

Mycobacterium tuberculosis; Q203; TB47; cryo-electron microscopy; cytochrome bcc complex; molecular biophysics; structural biology.

Figures
Products
嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z