Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Enzyme discovery could help in fight against TB

12.07.2018

An enzyme structure discovery made by scientists at the University of Warwick could help to eradicate tuberculosis

Research by a team led by Dr Elizabeth Fullam, has revealed new findings about an enzyme found in Mycobacterium tuberculosis (Mtb) the bacterium that causes TB.


NagA protein crystals.

Credit: University of Warwick

TB causes more deaths than any other infectious disease, including from HIV and malaria. In 2016 there were 10.4 million new cases of TB and 1.7 million people died. The rise in cases of TB that are resistant to the current therapies that are available means that there is an urgent need to develop new TB therapeutics.

Mtb is a highly unique bacterium and is enclosed within a distinctive cell wall that is comprised of unusual sugars and lipids which protect the bacteria from the host environment. Disruption of essential pathways involved in the assembly of the Mtb cell wall is an attractive approach for new TB drugs.

The team found a key structural motif in the tuberculosis N-acetylglucosamine-6-phosphate deacetylase (NagA) enzyme. Attacking this structural motif through the design and exploitation of new molecules will enable scientists to inhibit this critical pathway and kill TB.

Using the X-ray facilities at the Diamond Light Source, Harwell, they were provided with detailed molecular insights into how the NagA enzyme generates important precursors that are involved in Mtb cell wall biosynthesis and metabolism.

Dr Fullam, who is a Sir Henry Dale Fellow at the University of Warwick's School of Life Sciences, said: "Tuberculosis is a major global health problem and the current drugs that we use today are over 40 years old. It is therefore vital that we discover new therapeutic agents to combat TB. In our studies, we have investigated the role of an enzyme in Mtb called NagA. This enzyme is a promising drug target as it is at a crucial metabolic chokepoint in Mtb. This means that a molecule that stops the enzyme from working would be an effective strategy for a drug and therefore it is critical to understand its function.

"Our group has identified a weak point within this protein that we can target and will now enable us to design specific molecules to block its function"

Using a range of biochemical and biophysical checks to determine the substrate specificity for the Mtb NagA enzyme they found a unique structural feauture in the Mtb NagA enzyme.This has revealed a molecular image of the protein and provides a platform to allow scientists to design new drugs that will hopefully inhibit this vital pathway and kill TB.

The research 'Structural and functional determination of homologs of the Mycobacterium tuberculosis N-acetylglucosamine-6-phosphate deacetylase (NagA)' is published in the Journal of Biological Chemistry

###

For more information contact Nicola Jones, Media Relations Manager, University of Warwick N.Jones.1@warwick.ac.uk or 07920531221

Photo caption1 NagA protein crystals

Notes to Editors

Structural and functional determination of homologs of the Mycobacterium tuberculosis N-acetylglucosamine-6-phosphate deacetylase (NagA)' is published in the Journal of Biological Chemistry

DOI.1074/jbc.RA118.002597

Authors

Mohd Syed Ahangar, School of Life Sciences, University of Warwick, Warwick, Coventry CV4 7AL, United Kingdom
Christopher M. Furze, School of Life Sciences, University of Warwick, Warwick, Coventry CV4 7AL, United Kingdom
Collette S. Guy, School of Life Sciences, University of Warwick, Warwick, Coventry CV4 7AL, United Kingdom; Department of Chemistry, University of Warwick, Warwick, Coventry CV4 7AL, United Kingdom
Charlotte Cooper, School of Life Sciences, University of Warwick, Warwick, Coventry CV4 7AL, United Kingdom
Kathryn S. Maskew, School of Life Sciences, University of Warwick, Warwick, Coventry CV4 7AL, United Kingdom
Ben Graham, Department of Chemistry, University of Warwick, Warwick, Coventry CV4 7AL, United Kingdom
Alexander D. Cameron, School of Life Sciences
Elizabeth Fullam, School of Life Sciences, University of Warwick, Warwick, Coventry CV4 7AL, United Kingdom

Funding

This work was supported by a Sir Henry Dale Fellowship (to E. F.) jointly funded by the Wellcome Trust and Royal Society Grant 104193/Z/14/Z, Wellcome Trust Grant 201442/Z/16/Z (to E. F.), Royal Society Research Grant RG120405 (to E. F.), and Wellcome Warwick Quantitative Biomedicine Programme Institution Strategic Support Fund Seed Grant 105627/Z/14/Z; a Midlands Doctoral Training Partnership Studentship BB/M01116X/ 1 (to C. C.); this work was also supported in part by Warwick Integrative Synthetic Biology research technology platform (Grant BB/M017982/1)

You have received this email because the University of Warwick Press and Media Relations team believes its content is of interest and relevance to you as a member of the media.

We are committed to keeping your personal information safe and secure. Full details on how we use your personal data are given in our privacy notice.

If you would prefer not to be contacted by members of the Press and Media Relations team about news we believe is of professional interest to you, please email press@warwick.ac.uk to let us know.

Media Contact

Nicola Jones
N.Jones.1@warwick.ac.uk
07-920-531-221

 @warwicknewsroom

http://www.warwick.ac.uk 

Nicola Jones | EurekAlert!
Further information:
https://warwick.ac.uk/newsandevents/pressreleases/enzyme_discovery_could/

More articles from Life Sciences:

nachricht Scientists discover how the molecule-sorting station in our cells is formed and maintained
18.11.2019 | Tokyo University of Science

nachricht Pesticides: Improved effect prediction of low toxicant concentrations
18.11.2019 | Helmholtz Centre for Environmental Research - UFZ

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Images from NJIT's big bear solar observatory peel away layers of a stellar mystery

An international team of scientists, including three researchers from New Jersey Institute of Technology (NJIT), has shed new light on one of the central mysteries of solar physics: how energy from the Sun is transferred to the star's upper atmosphere, heating it to 1 million degrees Fahrenheit and higher in some regions, temperatures that are vastly hotter than the Sun's surface.

With new images from NJIT's Big Bear Solar Observatory (BBSO), the researchers have revealed in groundbreaking, granular detail what appears to be a likely...

Im Focus: New opportunities in additive manufacturing presented

Fraunhofer IFAM Dresden demonstrates manufacturing of copper components

The Fraunhofer Institute for Manufacturing Technology and Advanced Materials IFAM in Dresden has succeeded in using Selective Electron Beam Melting (SEBM) to...

Im Focus: New Pitt research finds carbon nanotubes show a love/hate relationship with water

Carbon nanotubes (CNTs) are valuable for a wide variety of applications. Made of graphene sheets rolled into tubes 10,000 times smaller than a human hair, CNTs have an exceptional strength-to-mass ratio and excellent thermal and electrical properties. These features make them ideal for a range of applications, including supercapacitors, interconnects, adhesives, particle trapping and structural color.

New research reveals even more potential for CNTs: as a coating, they can both repel and hold water in place, a useful property for applications like printing,...

Im Focus: Magnets for the second dimension

If you've ever tried to put several really strong, small cube magnets right next to each other on a magnetic board, you'll know that you just can't do it. What happens is that the magnets always arrange themselves in a column sticking out vertically from the magnetic board. Moreover, it's almost impossible to join several rows of these magnets together to form a flat surface. That's because magnets are dipolar. Equal poles repel each other, with the north pole of one magnet always attaching itself to the south pole of another and vice versa. This explains why they form a column with all the magnets aligned the same way.

Now, scientists at ETH Zurich have managed to create magnetic building blocks in the shape of cubes that - for the first time ever - can be joined together to...

Im Focus: A new quantum data classification protocol brings us nearer to a future 'quantum internet'

The algorithm represents a first step in the automated learning of quantum information networks

Quantum-based communication and computation technologies promise unprecedented applications, such as unconditionally secure communications, ultra-precise...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

First International Conference on Agrophotovoltaics in August 2020

15.11.2019 | Event News

Laser Symposium on Electromobility in Aachen: trends for the mobility revolution

15.11.2019 | Event News

High entropy alloys for hot turbines and tireless metal-forming presses

05.11.2019 | Event News

 
Latest News

Volcanoes under pressure

18.11.2019 | Earth Sciences

Scientists discover how the molecule-sorting station in our cells is formed and maintained

18.11.2019 | Life Sciences

Hot electrons harvested without tricks

18.11.2019 | Power and Electrical Engineering

VideoLinks
Science & Research
Overview of more VideoLinks >>>