Corporate Banner
Satellite Banner
Scientific Communities
Become a Member | Sign in
Home>News>This Article

Multi-tasking Protein Provides New Approaches for Anti-tuberculosis Drugs

Published: Thursday, February 17, 2011
Last Updated: Thursday, February 17, 2011
Bookmark and Share
Scientists from EMBL reveal new insights into the workings of enzymes from a group of bacteria including Mycobacterium tuberculosis.

In a paper published in PNAS, scientists from the European Molecular Biology Laboratory (EMBL) in Hamburg, Germany, reveal new insights into the workings of enzymes from a group of bacteria including Mycobacterium tuberculosis, the bacterium that causes tuberculosis.

The new findings present possible new opportunities for developing organism-specific drugs, which target the pathogen but leave other microorganisms, which are beneficial to us, untouched.

Tuberculosis remains one of the largest threats to human health worldwide, and one of the most frequent causes of death in HIV patients. With the increasing emergence of strains of Mycobacterium tuberculosis that are hyper-resistant to drugs, it becomes ever more urgent that novel treatments be developed, and the search for novel strategies for drug development is an important step in this process.

In the current study, Matthias Wilmanns and his group at EMBL identified a multi-tasking enzyme from Mycobacterium tuberculosis that catalyses reactions on two different molecules, or substrates. In most organisms, cells need two specific enzymes, known as HisA and TrpF, in order to produce two essential amino acids - histidine and tryptophan.

However, in Mycobacterium tuberculosis, the encoding gene for TrpF is missing, and the two reactions are instead catalyzed by a single enzyme, which is able to recognize and bind to two different substrates. This enzyme is known as PriA.

Using the Mycobacterium tuberculosis version of the PriA enzyme as a model, the researchers were able to unravel the hitherto unknown mechanism of bi-substrate specific binding observed in this group of bacteria.

“When we solved the three-dimensional structure of PriA, we found that it has the unique ability to form two different substrate-specific active sites,” Wilmanns says: “it can form a reaction-specific active site, or undergo what we call ‘substrate-induced metamorphosis’ to form a different active site.”

To further verify these observations, Wilmanns and colleagues screened 20,000 small molecule compounds, and identified a handful which inhibited both PriA-catalysed reactions but had no effect on TrpF activity.

“We believe that this ability for bi-substrate catalysis in Mycobacterium tuberculosis could be a new opportunity for future drug development,” Wilmanns concludes: “This organism-specific reaction process could be exploited, since only the pathogen but none of the other bacteria living in or on humans, many of which are important for our well being, would be targeted.”

Further Information
Access to this exclusive content is for Technology Networks Premium members only.

Join Technology Networks Premium for free access to:

  • Exclusive articles
  • Presentations from international conferences
  • Over 2,800+ scientific posters on ePosters
  • More Than 4,000+ scientific videos on LabTube
  • 35 community eNewsletters

Sign In

Forgotten your details? Click Here
If you are not a member you can join here

*Please note: By logging into you agree to accept the use of cookies. To find out more about the cookies we use and how to delete them, see our privacy policy.

Related Content

Finding Links and Missing Genes
A catalogue of large-scale genetic changes around the world.
Tuesday, October 06, 2015
Ages Apart
Multifaceted approach measured how brain and liver age differently.
Saturday, September 19, 2015
Iron Regulators Join War on Pathogens
Iron regulatory proteins (IRPs) play an important role in the body’s immune system.
Friday, July 17, 2015
EMBL Scientists Solve Decades-Old Cell Biology Puzzle
Behaviour of clathrin proteins, crucial for endocytosis, is clarified using new imaging techniques.
Saturday, June 20, 2015
It Runs in the Family
Distantly related viruses share a common machinery for replication.
Saturday, May 23, 2015
The Battle for Iron
Understanding anaemias of the chronically ill.
Saturday, February 07, 2015
Protecting us from Our Cells
Growth factor boosts natural defence against auto-immune disorders.
Tuesday, November 04, 2014
Double Act: How a Single Molecule Can Attract and Repel Growing Brain Connections
The 3D structure of Netrin-1 bound to DCC shows Netrin-1 binds to two DCC molecules in different ways.
Saturday, August 09, 2014
Cancer by Remote-Control
Overlooked DNA shuffling drives deadly paediatric brain tumour.
Tuesday, June 24, 2014
Wired for Change
First steps of gene regulation evolution revealed.
Monday, August 05, 2013
More than Meets the Eye
‘Transformer’ protein makes different sized transport pods.
Tuesday, May 29, 2012
Rigged to Explode?
Inherited mutation links exploding chromosomes to cancer.
Wednesday, April 11, 2012
The Human Genome’s Breaking Points
Comprehensive catalogue uncovers genetic sequence of large-scale differences between human genomes.
Wednesday, February 16, 2011
EMBL Scientists Uncover Counterpart of Cerebral Cortex in Marine Worms
Findings give an idea of what the most ancient higher brain centres looked like, and what our distant ancestors used them for.
Friday, September 03, 2010
EMBL Scientists Identify Proteins that Ensure Iron Balance
Researchers discover that newly found group of proteins are required for the functioning of mitochondria, the cell’s energy factories.
Monday, August 09, 2010
Scientific News
High Throughput Mass Spectrometry-Based Screening Assay Trends
Dr John Comley provides an insight into HT MS-based screening with a focus on future user requirements and preferences.
The MaxSignal Colistin ELISA Test Kit from Bioo Scientific
Kit can help prevent the antibiotic apocalypse by keeping last resort drugs out of the food supply.
Kitchen Utensils Can Spread Bacteria Between Foods
In a recent study researchers found that produce that contained bacteria would contaminate other produce items through the continued use of knives or graters—the bacteria would latch on to the utensils commonly found in consumers' homes and spread to the next item.
Exploring the Causes of Cancer
Queen's research to understand the regulation of a cell surface protein involved in cancer.
Safer, Faster Way To Remove Pollutants From Water
Using nanoparticles filled with enzymes proves more effective than current methods.
Drug May Prevent Life-Threatening Muscle Loss in Advanced Cancers
New data describes how an experimental drug can stop life-threatening muscle wasting (cachexia) associated with advanced cancers and restore muscle health.
Ancient Viral Molecules Essential for Human Development
Genetic material from ancient viral infections is critical to human development, according to researchers at the Stanford University School of Medicine.
Novel Tumor Treatment
In the first published results from a $386,000 National Cancer Institute grant awarded earlier this year, a paper by Scott Verbridge and Rafael Davalos has been published.
Speeding Up the Process of Making Vaccines
System uses a freeze-dry concept to develop "just-add-water" solution.
Chemical Design Made Easier
Rice University scientists prepare elusive organocatalysts for drug and fine chemical synthesis.
Scroll Up
Scroll Down
Skyscraper Banner

Skyscraper Banner
Go to LabTube
Go to eposters
Access to the latest scientific news
Exclusive articles
Upload and share your posters on ePosters
Latest presentations and webinars
View a library of 1,800+ scientific and medical posters
2,800+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
4,000+ scientific videos