Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Johns Hopkins team finds new way to attack TB

25.03.2010
Suspecting that a particular protein in tuberculosis was likely to be vital to the bacteria's survival, Johns Hopkins scientists screened 175,000 small chemical compounds and identified a potent class of compounds that selectively slows down this protein's activity and, in a test tube, blocks TB growth, demonstrating that the protein is indeed a vulnerable target.

This class of chemical compounds attacks TB by inhibiting methionine aminopeptidase (MetAP), an essential enzyme found in organisms ranging from bacteria to humans, and that clearly has been conserved throughout evolution because of its important task of ensuring the proper manufacture of proteins.

"The MetAP inhibitors we discovered are hits, or leads in the sense that they provide a framework — a starting point — for the future development of an anti-TB drug," says Jun O. Liu, Ph.D., professor of pharmacology and molecular sciences, Johns Hopkins University School of Medicine.

The research appears in the January 29 edition of Chemistry & Biology.

The scientists cautioned that although the MetAP inhibitors prevent TB growth in test tubes, they have a long way to go before being declared safe and effective to treat TB patients. To understand how the MetAP inhibitors work, Liu suggests thinking of proteins as a strand of pearls folded in unique 3-D shapes, with each bead representing a protein building block, or amino acid. Invariably, the first bead, or amino acid, in every string, whether human or bacterial protein, is a methionine. The methionine ultimately needs to be removed in order for the protein to mature and fold correctly. Its removal is the job of enzymes called methionine aminopeptidases, or MetAPs.

"If you knock out this enzyme in TB bacteria, the bacteria will not survive," Liu says. "We expected that would happen, and confirmed it by manipulating how much enzyme is expressed to see what happens to the sensitivity of the bacteria when inhibitors are present."

What caught the team by surprise, however, was finding a potent class of compounds (called 2,3-dichloro-1, 4-naphthoquinone) that inhibits this enzyme. That discovery involved the use of large-scale, high-throughput screening of 175,000 compounds and measuring the potencies of a dozen related hits against the enzyme.

The final experiment by the team was to test the MetAP inhibitors on TB bacteria in culture to see if it had any effect on bacteria growth.

"Judging from potency, a MetAP inhibibitor alone probably won't wipe out TB," Liu says. "TB is so hard to treat that the standard therapy involves a cocktail of multiple drugs; no single compound is powerful enough. Our hope is that someday an inhibitor of MetAP will become a new component to enhance the existing therapy."

This study was funded by the National Institutes of Health.

In addition to Liu, authors of this paper are Omonike Olaleye, Tirumalai R. Raghunand, Shridhar Bhat, Sandeep Tyagi, Gyanu Lamichhane, Peihua Gu, Jiangbing Zhou, Ying Zhang, Jacques Grosset, and William R. Bishai, all of Johns Hopkins.

Maryalice Yakutchik | EurekAlert!
Further information:
http://www.jhmi.edu

Further reports about: MetAP MetAP inhibitors TB TB bacteria amino acid bacteria methionine aminopeptidase

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 >>>