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Tuberculosis (TB) is a contagious bacterial infection that mainly affects the lungs and can spread through the air from person to person. In 2019, it was reported to affect nearly 5,000 people a year in the UK1.
Part of the UK Health Security Agency’s current TB Action Plan for England is to ensure access to appropriate anti-TB medications, preparations and newer drugs for adults and children2.
The frontline TB drug ethambutol is an antibiotic that prevents growth of the tuberculous bacteria in the body. It’s been in use since the 1960s3 but its mode of action has not been clear. Molecular structural detail of the TB bacterium is required to gain insight into exactly how the drug functions.
The Diamond synchrotron provides incredibly bright light that can be used to investigate matter at the molecular scale – enabling scientists to ‘see inside’ their objects of study.
An international group of Chinese, Australian and UK researchers used Diamond’s intense X-rays to determine the detailed crystal structure of a TB-causing bacterial complex, Mycobacterium tuberculosis (Mtb).
The bacterium is able to build a complex cell wall to protect and support itself. The anti-TB drug ethambutol inhibits synthesis of the bacterial cell wall by targeting certain key proteins, including the EmbC protein. This protein is integral to the synthesis of the bacterial wall and was the focus of the study.
The team discovered compelling new information on the binding capacity of the EmbC protein. With support from Diamond’s I04-1 beamline, the crystal structure of a EmbC protein complex has been determined, giving insight into how ethambutol binds to it.
Combining this information with data gathered from other techniques provides a structural basis for understanding the biochemical function and inhibition of EmbC and for the exciting development of new anti-TB agents.
Tuberculosis cases in England hit lowest ever levels - GOV.UK (www.gov.uk)
Zhang L. et al. Structures of cell wall arabinosyltransferases with the anti-tuberculosis drug ethambutol. Science 368 (April 2020). DOI: 10.1126/science.aba9102
The fixed wavelength monochromatic macromolecular crystallography (MX) beamline I04-1.
Diamond press office: Isabelle Boscaro-Clarke, Head of Communications, [email protected]
Beamline I04-1: Frank von Delft, Principal Beamline Scientist, [email protected]
Corresponding author: Lu Zhang, Shanghai Tech University, [email protected]
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