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 New eDNA technology used to quickly assess coral reefs
18.04.2019 | University of Hawaii at Manoa

nachricht New automated biological-sample analysis systems to accelerate disease detection
18.04.2019 | Polytechnique Montréal

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Explosion on Jupiter-sized star 10 times more powerful than ever seen on our sun

A stellar flare 10 times more powerful than anything seen on our sun has burst from an ultracool star almost the same size as Jupiter

  • Coolest and smallest star to produce a superflare found
  • Star is a tenth of the radius of our Sun
  • Researchers led by University of Warwick could only see...

Im Focus: Quantum simulation more stable than expected

A localization phenomenon boosts the accuracy of solving quantum many-body problems with quantum computers which are otherwise challenging for conventional computers. This brings such digital quantum simulation within reach on quantum devices available today.

Quantum computers promise to solve certain computational problems exponentially faster than any classical machine. “A particularly promising application is the...

Im Focus: Largest, fastest array of microscopic 'traffic cops' for optical communications

The technology could revolutionize how information travels through data centers and artificial intelligence networks

Engineers at the University of California, Berkeley have built a new photonic switch that can control the direction of light passing through optical fibers...

Im Focus: A long-distance relationship in femtoseconds

Physicists observe how electron-hole pairs drift apart at ultrafast speed, but still remain strongly bound.

Modern electronics relies on ultrafast charge motion on ever shorter length scales. Physicists from Regensburg and Gothenburg have now succeeded in resolving a...

Im Focus: Researchers 3D print metamaterials with novel optical properties

Engineers create novel optical devices, including a moth eye-inspired omnidirectional microwave antenna

A team of engineers at Tufts University has developed a series of 3D printed metamaterials with unique microwave or optical properties that go beyond what is...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Revered mathematicians and computer scientists converge with 200 young researchers in Heidelberg!

17.04.2019 | Event News

First dust conference in the Central Asian part of the earth’s dust belt

15.04.2019 | Event News

Fraunhofer FHR at the IEEE Radar Conference 2019 in Boston, USA

09.04.2019 | Event News

 
Latest News

New automated biological-sample analysis systems to accelerate disease detection

18.04.2019 | Life Sciences

Explosion on Jupiter-sized star 10 times more powerful than ever seen on our sun

18.04.2019 | Physics and Astronomy

New eDNA technology used to quickly assess coral reefs

18.04.2019 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>