Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Carb Synthesis Sheds Light on Promising Tuberculosis Drug Target

24.06.2009
A fundamental question about how sugar units are strung together into long carbohydrate chains has also pinpointed a promising way to target new medicines against tuberculosis.

Working with components of the tuberculosis bacterium, researchers from the University of Wisconsin-Madison identified an unusual process by which the pathogen builds an important structural carbohydrate.

In addition to its implications for human health, the mechanism offers insight into a widespread but poorly understood basic biological function — controlling the length of carbohydrate polymers.

“Carbohydrate polymers are the most abundant organic molecules on the planet, and it’s amazing that we don’t know more about these are made,” says Laura Kiessling, a professor of chemistry and biochemistry at UW-Madison. “There’s not much known about how length is controlled in these carbohydrate polymers.”

Kiessling is senior author, along with graduate students John May and Rebecca Splain and postdoctoral fellow Christine Brotschi, of a new study appearing in the online Early Edition of the Proceedings of the National Academy of Sciences the week of June 22.

Most carbohydrates exist as many sugar molecules linked into long chains, or polymers. The right number of sugars in the chain is vital for them to work properly, but different types of carbohydrate polymers range from a few dozen sugars in some bacterial molecules to tens of thousands of sugar links in cellulose, a common plant material.

Despite its importance, it's not clear how carbohydrate length is determined, Kiessling says. Unlike some biological chains — such as DNA and proteins — that are built off a template that guides the length of the final product, carbohydrate-synthesizing enzymes work without templates.

“Nature has strategies to generate polymers of different lengths, but we know very little about those strategies,” she says. “If you make something too short, it’s probably not going to function in the role that you want, and if you make something too long, you’re wasting energy that you need to use elsewhere.”

The research team focused on an enzyme called GlfT2 that is responsible for building a critical carbohydrate component of the TB bacterial cell wall.

The researchers found that a small fatty component at the starting end binds to the enzyme and helps it track the length of the growing polymer. As the enzyme adds more and more sugar units to the opposite end, the chain becomes increasingly unwieldy.

“If the chain gets too long, it gets hard to hold on to both of the ends, so the chain falls off” the synthesizing enzyme, Kiessling says, forming a completed carbohydrate polymer.

The researchers believe that the enzymes responsible for building different types of carbohydrates exceed their comfort level at different points, leading to molecules of different prescribed lengths.

The current report is the first description of this “tethering” mechanism — named for the fatty lipid that tethers the start of the polymer to the enzyme — in carbohydrate synthesis, Kiessling says, though it may prove to be common among other organisms as well.

In addition to providing insight into what may be a general mechanism for designing and building carbohydrates, the work gives insight into developing new therapeutics against TB. The GlfT2 enzyme is essential for bacterial survival and growth but has never yet been targeted by potential treatment methods. Knowing that the enzyme has two binding sites — one for each end of the growing carbohydrate — makes it an especially appealing candidate.

“Our mechanism provides a blueprint for strategies to block a new anti-mycobacterial target,” Kiessling says.

New drug targets will be critical in the fight against tuberculosis, as drug-resistant strains are becoming increasingly widespread. The carbohydrate-synthesizing enzyme represents an untapped and promising resource for crippling even strains that are resistant to current drugs.

The prevalence of carbohydrate polymers in biological systems also means that understanding how their length is controlled has many possible applications, ranging from designing more potent and effective vaccines to facilitating the production of useful fuels from plant materials.

“It’s a nice illustration of how basic research can lead to applications that are very practical,” says Kiessling.

The research was funded by the National Institutes of Health, National Science Foundation, American Chemical Society and Swiss National Science Foundation.

Laura Kiessling | Newswise Science News
Further information:
http://www.wisc.edu

More articles from Health and Medicine:

nachricht Correct connections are crucial
26.06.2017 | Charité - Universitätsmedizin Berlin

nachricht One gene closer to regenerative therapy for muscular disorders
01.06.2017 | Cincinnati Children's Hospital Medical Center

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

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

Im Focus: Can we see monkeys from space? Emerging technologies to map biodiversity

An international team of scientists has proposed a new multi-disciplinary approach in which an array of new technologies will allow us to map biodiversity and the risks that wildlife is facing at the scale of whole landscapes. The findings are published in Nature Ecology and Evolution. This international research is led by the Kunming Institute of Zoology from China, University of East Anglia, University of Leicester and the Leibniz Institute for Zoo and Wildlife Research.

Using a combination of satellite and ground data, the team proposes that it is now possible to map biodiversity with an accuracy that has not been previously...

Im Focus: Climate satellite: Tracking methane with robust laser technology

Heatwaves in the Arctic, longer periods of vegetation in Europe, severe floods in West Africa – starting in 2021, scientists want to explore the emissions of the greenhouse gas methane with the German-French satellite MERLIN. This is made possible by a new robust laser system of the Fraunhofer Institute for Laser Technology ILT in Aachen, which achieves unprecedented measurement accuracy.

Methane is primarily the result of the decomposition of organic matter. The gas has a 25 times greater warming potential than carbon dioxide, but is not as...

Im Focus: How protons move through a fuel cell

Hydrogen is regarded as the energy source of the future: It is produced with solar power and can be used to generate heat and electricity in fuel cells. Empa researchers have now succeeded in decoding the movement of hydrogen ions in crystals – a key step towards more efficient energy conversion in the hydrogen industry of tomorrow.

As charge carriers, electrons and ions play the leading role in electrochemical energy storage devices and converters such as batteries and fuel cells. Proton...

Im Focus: A unique data centre for cosmological simulations

Scientists from the Excellence Cluster Universe at the Ludwig-Maximilians-Universität Munich have establised "Cosmowebportal", a unique data centre for cosmological simulations located at the Leibniz Supercomputing Centre (LRZ) of the Bavarian Academy of Sciences. The complete results of a series of large hydrodynamical cosmological simulations are available, with data volumes typically exceeding several hundred terabytes. Scientists worldwide can interactively explore these complex simulations via a web interface and directly access the results.

With current telescopes, scientists can observe our Universe’s galaxies and galaxy clusters and their distribution along an invisible cosmic web. From the...

Im Focus: Scientists develop molecular thermometer for contactless measurement using infrared light

Temperature measurements possible even on the smallest scale / Molecular ruby for use in material sciences, biology, and medicine

Chemists at Johannes Gutenberg University Mainz (JGU) in cooperation with researchers of the German Federal Institute for Materials Research and Testing (BAM)...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Plants are networkers

19.06.2017 | Event News

Digital Survival Training for Executives

13.06.2017 | Event News

Global Learning Council Summit 2017

13.06.2017 | Event News

 
Latest News

Study shines light on brain cells that coordinate movement

26.06.2017 | Life Sciences

Smooth propagation of spin waves using gold

26.06.2017 | Physics and Astronomy

Switchable DNA mini-machines store information

26.06.2017 | Information Technology

VideoLinks
B2B-VideoLinks
More VideoLinks >>>