Featured Research

from universities, journals, and other organizations

Two in one: Multi-tasking protein provides new approaches for anti-tuberculosis drugs

Date:
February 15, 2011
Source:
European Molecular Biology Laboratory (EMBL)
Summary:
Scientists have revealed new insights into the workings of an enzyme from Mycobacterium tuberculosis, the bacterium that causes tuberculosis. The findings present new opportunities for developing organism-specific drugs, which target the pathogen but leave other microorganisms, which are beneficial to us, untouched.

Mycobacterium tuberculosis’ enzyme PriA has the unique ability to alter its active site depending on which of two molecules it is interacting with.
Credit: EMBL/Felix List

Scientists from the European Molecular Biology Laboratory (EMBL) in Hamburg, Germany, have revealed new insights into the workings of enzymes from a group of bacteria including Mycobacterium tuberculosis, the bacterium that causes tuberculosis. The findings present possible new opportunities for developing organism-specific drugs, which target the pathogen but leave other microorganisms, which are beneficial to us, untouched.

The research was published in the Proceedings of the National Academy of Sciences.

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 catalysed 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."


Story Source:

The above story is based on materials provided by European Molecular Biology Laboratory (EMBL). Note: Materials may be edited for content and length.


Journal Reference:

  1. A. V. Due, J. Kuper, A. Geerlof, J. P. v. Kries, M. Wilmanns. Bisubstrate specificity in histidine/tryptophan biosynthesis isomerase from Mycobacterium tuberculosis by active site metamorphosis. Proceedings of the National Academy of Sciences, 2011; DOI: 10.1073/pnas.1015996108

Cite This Page:

European Molecular Biology Laboratory (EMBL). "Two in one: Multi-tasking protein provides new approaches for anti-tuberculosis drugs." ScienceDaily. ScienceDaily, 15 February 2011. <www.sciencedaily.com/releases/2011/02/110215081926.htm>.
European Molecular Biology Laboratory (EMBL). (2011, February 15). Two in one: Multi-tasking protein provides new approaches for anti-tuberculosis drugs. ScienceDaily. Retrieved July 23, 2014 from www.sciencedaily.com/releases/2011/02/110215081926.htm
European Molecular Biology Laboratory (EMBL). "Two in one: Multi-tasking protein provides new approaches for anti-tuberculosis drugs." ScienceDaily. www.sciencedaily.com/releases/2011/02/110215081926.htm (accessed July 23, 2014).

Share This




More Health & Medicine News

Wednesday, July 23, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Courts Conflicted Over Healthcare Law

Courts Conflicted Over Healthcare Law

AP (July 22, 2014) Two federal appeals courts issued conflicting rulings Tuesday on the legality of the federally-run healthcare exchange that operates in 36 states. (July 22) Video provided by AP
Powered by NewsLook.com
Why Do People Believe We Only Use 10 Percent Of Our Brains?

Why Do People Believe We Only Use 10 Percent Of Our Brains?

Newsy (July 22, 2014) The new sci-fi thriller "Lucy" is making people question whether we really use all our brainpower. But, as scientists have insisted for years, we do. Video provided by Newsy
Powered by NewsLook.com
Scientists Find New Way To Make Human Platelets

Scientists Find New Way To Make Human Platelets

Newsy (July 22, 2014) Boston scientists have discovered a new way to create fully functioning human platelets using a bioreactor and human stem cells. Video provided by Newsy
Powered by NewsLook.com
Gilead's $1000-a-Pill Drug Could Cure Hep C in HIV-Positive People

Gilead's $1000-a-Pill Drug Could Cure Hep C in HIV-Positive People

TheStreet (July 21, 2014) New research shows Gilead Science's drug Sovaldi helps in curing hepatitis C in those who suffer from HIV. In a medical study, the combination of Gilead's Hep C drug with anti-viral drug Ribavirin cured 76% of HIV-positive patients suffering from the most common hepatitis C strain. Hepatitis C and related complications have been a top cause of death in HIV-positive patients. Typical medication used to treat the disease, including interferon proteins, tended to react badly with HIV drugs. However, Sovaldi's %1,000-a-pill price tag could limit the number of patients able to access the treatment. TheStreet's Keris Lahiff reports from New York. Video provided by TheStreet
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins