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 How cancer metastasis happens: Researchers reveal a key mechanism
19.01.2018 | Weill Cornell Medicine

nachricht Researchers identify new way to unmask melanoma cells to the immune system
17.01.2018 | Duke University 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: Artificial agent designs quantum experiments

On the way to an intelligent laboratory, physicists from Innsbruck and Vienna present an artificial agent that autonomously designs quantum experiments. In initial experiments, the system has independently (re)discovered experimental techniques that are nowadays standard in modern quantum optical laboratories. This shows how machines could play a more creative role in research in the future.

We carry smartphones in our pockets, the streets are dotted with semi-autonomous cars, but in the research laboratory experiments are still being designed by...

Im Focus: Scientists decipher key principle behind reaction of metalloenzymes

So-called pre-distorted states accelerate photochemical reactions too

What enables electrons to be transferred swiftly, for example during photosynthesis? An interdisciplinary team of researchers has worked out the details of how...

Im Focus: The first precise measurement of a single molecule's effective charge

For the first time, scientists have precisely measured the effective electrical charge of a single molecule in solution. This fundamental insight of an SNSF Professor could also pave the way for future medical diagnostics.

Electrical charge is one of the key properties that allows molecules to interact. Life itself depends on this phenomenon: many biological processes involve...

Im Focus: Paradigm shift in Paris: Encouraging an holistic view of laser machining

At the JEC World Composite Show in Paris in March 2018, the Fraunhofer Institute for Laser Technology ILT will be focusing on the latest trends and innovations in laser machining of composites. Among other things, researchers at the booth shared with the Aachen Center for Integrative Lightweight Production (AZL) will demonstrate how lasers can be used for joining, structuring, cutting and drilling composite materials.

No other industry has attracted as much public attention to composite materials as the automotive industry, which along with the aerospace industry is a driver...

Im Focus: Room-temperature multiferroic thin films and their properties

Scientists at Tokyo Institute of Technology (Tokyo Tech) and Tohoku University have developed high-quality GFO epitaxial films and systematically investigated their ferroelectric and ferromagnetic properties. They also demonstrated the room-temperature magnetocapacitance effects of these GFO thin films.

Multiferroic materials show magnetically driven ferroelectricity. They are attracting increasing attention because of their fascinating properties such as...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

10th International Symposium: “Advanced Battery Power – Kraftwerk Batterie” Münster, 10-11 April 2018

08.01.2018 | Event News

See, understand and experience the work of the future

11.12.2017 | Event News

Innovative strategies to tackle parasitic worms

08.12.2017 | Event News

 
Latest News

Let the good tubes roll

19.01.2018 | Materials Sciences

How cancer metastasis happens: Researchers reveal a key mechanism

19.01.2018 | Health and Medicine

Meteoritic stardust unlocks timing of supernova dust formation

19.01.2018 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>