Structures of cell wall arabinosyltransferases with the anti-tuberculosis drug ethambutol

Journal: Science

Published: 2020-06-12

DOI: 10.1126/science.aba9102

Affiliations: 15

Authors: 27

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Research Highlight

Towards better tuberculosis drugs with structural biology



A structural analysis of how a widely prescribed anti-tuberculosis drug binds to its target could lead to the development of more-efficacious medicines.

Tuberculosis kills about 1.5 million people globally each year. The drug ethambutol has been used to treat the disease for almost six decades, but some strains of the Mycobacterium tuberculosis — the infectious bacterium responsible for tuberculosis — have become resistant to it and other anti-tuberculosis drugs. Furthermore, scientists are not exactly sure how ethambutol attacks the bacterium.

Now, a ShanghaiTech University–led team has determined the three-dimensional structures of two enzyme complexes involved in synthesizing the cell wall of M. tuberculosis.

With each complex, the researchers determined how ethambutol interacts with the enzymes. They also showed how resistance mutations found in patients who took the drug impact the molecular binding of the anti-tuberculosis agent.

The findings should allow researchers to design next-generation, ethambutol-like drugs that are less susceptible to the same resistance mechanisms.

Supported content

  1. Science 368, 1211–1219 (2020). doi: 10.1126/science.aba9102
Institutions Share
Shanghai Institute for Advanced Immunochemical Studies (SIAIS), ShanghaiTech, China 0.17
iHuman Institute, ShanghaiTech, China 0.17
School of Life Science and Technology (SLST), ShanghaiTech, China 0.17
Institute of Microbiology and Infection (IMI), UB, United Kingdom (UK) 0.15
National Laboratory of Biomacromolecules (NLB), IBP CAS, China 0.04
CAS Key Laboratory of RNA Biology, IBP CAS, China 0.04
CAS Center for Excellence in Biomacromolecules, China 0.04
State Key Laboratory of Structural Biology, Tsinghua, China 0.04
School of Chemistry and Molecular Biosciences (SCMB), UQ, Australia 0.04
State Key Laboratory of Medicinal Chemical Biology (SKLMCB), NKU, China 0.03
Frontiers Science Center for Cell Response, NKU, China 0.03
College of Pharmacy, NKU, China 0.03
University of Chinese Academy of Sciences (UCAS), China 0.02
CAS Center for Excellence in Molecular Cell Science, SIBS CAS, China 0.01
Institute of Biochemistry and Cell Biology (IBCB), SIBS CAS, China 0.01