Featured Research

from universities, journals, and other organizations

Two new weapons in the battle against bacteria

Date:
February 13, 2014
Source:
Technische Universitaet Muenchen
Summary:
Proteases are vital proteins that serve for order within cells. They break apart other proteins, ensuring that these are properly synthesized and decomposed. Proteases are also responsible for the pathogenic effects of many kinds of bacteria. Now chemists have discovered two hitherto unknown mechanisms of action that can be used to permanently disarm an important bacterial protease.

The target: bacterial protease ClpP.
Credit: M. Gersch / TUM

Proteins are made up of a chain of amino acids and are vital for all cell processes. Proteases are among the most important types of protein. Like "molecular scissors," they cut other proteins at given positions and thereby execute important cell functions. By cutting the amino acid chains to the right length or breaking proteins apart they, for example, activate or deactivate proteins, decompose defective ones or switch signal sequences that serve to transport proteins to their proper position within a cell.

But proteases are important not only for human cells -- bacteria also rely on them. There are hardly any effective antibiotics left in the fight against pathogens like multi-resistant strains of Staphylococcus aureus bacteria or Mycobacterium tuberculosis which causes tuberculosis.

Researchers around the world are thus working ardently to find new ways of disarming the proteases in these strains to combat them. At the heart of this effort lies the so-called ClpP protease. It comprises 14 subunits and has a central regulatory function. The usual approach to deactivating this protease is to block all active centers of the ClpP. These are effectively the "cutting edges of the scissors," i.e. the portions of the protein that are responsible for breaking apart other proteins.

"However, the inhibitors used in the past have one decisive disadvantage," explains Stephan Sieber who heads the Chair for Organic Chemistry II at the Technische Universitaet Muenchen (TUM). "They don't permanently disarm the proteins, but only work for a few hours. On top of that, to be effective they must attack all active centers of the protein."

New strategies against bacteria

In collaboration with Professor Michael Groll, who heads the Chair for Biochemistry, Malte Gersch and Roman Kolb, doctoral candidates at Professor Sieber's chair, have succeeded in uncovering two completely new mechanisms that can be used to permanently deactivate these important bacteriological proteases -- in one case even without having to attack all active centers of the protein.

The first mechanism disrupts the arrangement of amino acids required for the cohesion of the protease subunits. As a result the protease breaks into two parts. The second acts directly on the core of the active center. It converts the amino acid that does the actual splitting into another kind of amino acid -- the "scissors" lose their edge and the protein is rendered inoperable. Both approaches inhibit the protease in completely novel ways and are thus very promising for the development of new forms of medication.

The scientists also found a whole series of inhibitors that initiate the two mechanisms. "Knowing the ways in which substances deactivate the proteases is a huge advance," says Gersch. "We can now optimize the substances and possibly also apply the principle to other proteases."

In further research, Gersch and Sieber plan to test their substances on living bacterial strains to determine if these are truly inhibited in growth and pathogenic effect. "Although the bacteria are not completely disarmed, they produce significantly fewer toxins that are conducive to inflammation," says Gersch. "The basic idea is that we give the immune system more time to handle the pathogens on its own while the formation of new resistances is suppressed."


Story Source:

The above story is based on materials provided by Technische Universitaet Muenchen. Note: Materials may be edited for content and length.


Journal Reference:

  1. Malte Gersch, Roman Kolb, Ferdinand Alte, Michael Groll, Stephan A. Sieber. Disruption of Oligomerization and Dehydroalanine Formation as Mechanisms for ClpP Protease Inhibition. Journal of the American Chemical Society, 2014; 136 (4): 1360 DOI: 10.1021/ja4082793

Cite This Page:

Technische Universitaet Muenchen. "Two new weapons in the battle against bacteria." ScienceDaily. ScienceDaily, 13 February 2014. <www.sciencedaily.com/releases/2014/02/140213122419.htm>.
Technische Universitaet Muenchen. (2014, February 13). Two new weapons in the battle against bacteria. ScienceDaily. Retrieved October 1, 2014 from www.sciencedaily.com/releases/2014/02/140213122419.htm
Technische Universitaet Muenchen. "Two new weapons in the battle against bacteria." ScienceDaily. www.sciencedaily.com/releases/2014/02/140213122419.htm (accessed October 1, 2014).

Share This



More Plants & Animals News

Wednesday, October 1, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Earth Has Lost Half Its Vertebrate Wildlife Since 1970: WWF

Earth Has Lost Half Its Vertebrate Wildlife Since 1970: WWF

Newsy (Sep. 30, 2014) A new study published by the World Wide Fund for Nature found that more than half of the world's wildlife population has declined since 1970. Video provided by Newsy
Powered by NewsLook.com
Dolphins Might Use Earth's Magnetic Field As A GPS

Dolphins Might Use Earth's Magnetic Field As A GPS

Newsy (Sep. 30, 2014) A study released Monday suggests dolphins might be able to sense the Earth's magnetic field and possibly use it as a means of navigation. Video provided by Newsy
Powered by NewsLook.com
How To Battle Stink Bug Season

How To Battle Stink Bug Season

Newsy (Sep. 30, 2014) Homeowners in 33 states grapple with stink bugs moving indoors at this time of year. Here are a few tips to avoid stink bug infestations. Video provided by Newsy
Powered by NewsLook.com
California University Designs Sustainable Winery

California University Designs Sustainable Winery

Reuters - US Online Video (Sep. 27, 2014) Amid California's worst drought in decades, scientists at UC Davis design a sustainable winery that includes a water recycling system. Vanessa Johnston reports. Video provided by Reuters
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:

Strange & Offbeat Stories


Plants & Animals

Earth & Climate

Fossils & Ruins

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