Featured Research

from universities, journals, and other organizations

New Compound Effectively Treats Fungal Infections

Date:
June 24, 2007
Source:
European Molecular Biology Laboratory
Summary:
The human body is home to many different kinds of fungi. While the majority normally do not harm us, some fungi can cause unpleasant infections of skin, nails or lungs. Now scientists have found a new mechanism to attack hard-to-treat fungal infections. They describe how a new compound kills fungal pathogens by blocking an enzyme crucial for their protein synthesis.

Crystal structure of the leucyl-tRNA synthetase bound to a tRNA and the compound AN2690.
Credit: Image courtesy of European Molecular Biology Laboratory

A new mechanism to attack hard-to-treat fungal infections has been revealed by scientists from the biotech company Anacor Pharmaceuticals Inc., California, and the European Molecular Biology Laboratory [EMBL] outstation in Grenoble, France. In the current issue of Science they describe how a new compound kills fungal pathogens by blocking an enzyme crucial for their protein synthesis.

The human body is home to many different kinds of fungi. While the majority normally do not harm us, some fungi can cause unpleasant infections of skin, nails or lungs.

"We have discovered a new compound that has the potential to treat common chronic nail infections caused by fungi," says Dickon Alley, researcher at Anacor Pharmaceuticals. "The compound, called AN2690, kills fungi by blocking their ability to make proteins. It has been very successful in clinical trials." AN2690 interferes with an enzyme called leucyl-tRNA synthetase, which is involved in translation, one of the last steps in the process of turning a gene's DNA code into a protein.

The process begins when the cell makes an RNA version of the gene's code, called messenger RNA. Ribosomes, the cell's protein synthesis machinery, then translate the messenger RNA into protein by stitching together the amino acids in the order specified by the message. This requires the help of molecules called tRNAs, which link the code of the messenger RNA to the correct amino acid.

Leucyl-tRNA synthetase is one of a group of enzymes called aminoacyl-tRNA synthetases that attach the correct amino acid to each tRNA. Some of these enzymes have two main functional parts, or active sites: a site that links the amino acid to the tRNA, and a separate editing site that proofreads this process and removes wrongly added amino acids.

To find out how exactly AN2690 blocks leucyl-tRNA synthetase Stephen Cusack, Head of EMBL Grenoble, and his team generated crystals of the enzyme bound to tRNA in the presence of AN2690. Examining them with the high-intensity X-ray source at the European Synchrotron Radiation Facility, Cusack and his colleagues found that AN2690 sticks in the editing site of the enzyme where it makes a very strong bond to the end of the tRNA, trapping it on the enzyme.

This stops the enzyme working and thus blocks protein synthesis, killing the fungal cell. The mechanism crucially depends on a boron atom that is part of AN2690, which is needed to link the compound to the tRNA. It is the first time that scientists describe such a mechanism, suggesting boron containing compounds as a promising new class of drug candidates.

"Now that we know how AN2690 works, the same approach could be adapted to target other aminoacyl-tRNA synthetases with editing sites and also other pathogenic microbes," concludes Cusack. "We are now working towards finding related antibacterial compounds that could help counter the problem of antibiotic resistance."

Reference: F.L. Rock, S. Cusack, M.R.K. Alley et al. An antifungal agent inhibits an aminoacyl-tRNA synhetase by trapping tRNA in the editing site, Science, 22 June 2007


Story Source:

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


Cite This Page:

European Molecular Biology Laboratory. "New Compound Effectively Treats Fungal Infections." ScienceDaily. ScienceDaily, 24 June 2007. <www.sciencedaily.com/releases/2007/06/070622101043.htm>.
European Molecular Biology Laboratory. (2007, June 24). New Compound Effectively Treats Fungal Infections. ScienceDaily. Retrieved September 20, 2014 from www.sciencedaily.com/releases/2007/06/070622101043.htm
European Molecular Biology Laboratory. "New Compound Effectively Treats Fungal Infections." ScienceDaily. www.sciencedaily.com/releases/2007/06/070622101043.htm (accessed September 20, 2014).

Share This



More Plants & Animals News

Saturday, September 20, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Chocolate Museum Opens in Brussels

Chocolate Museum Opens in Brussels

AFP (Sep. 19, 2014) Considered a "national heritage" in Belgium, chocolate now has a new museum in Brussels. In a former chocolate factory, visitors to the permanent exhibition spaces, workshops and tastings can discover derivatives of the cocoa bean. Duration: 01:00 Video provided by AFP
Powered by NewsLook.com
Could Grief Affect The Immune Systems Of Senior Citizens?

Could Grief Affect The Immune Systems Of Senior Citizens?

Newsy (Sep. 19, 2014) The study found elderly people are much more likely to become susceptible to infection than younger adults going though a similar situation. Video provided by Newsy
Powered by NewsLook.com
Jury Delivers Verdict in Salmonella Trial

Jury Delivers Verdict in Salmonella Trial

AP (Sep. 19, 2014) A federal jury has convicted three people in connection with an outbreak of salmonella poisoning five years ago that sickened hundreds of people and was linked to a number of deaths. (Sept. 19) Video provided by AP
Powered by NewsLook.com
Raw: Elephant Undergoes Surgery in Tbilisi Zoo

Raw: Elephant Undergoes Surgery in Tbilisi Zoo

AP (Sep. 18, 2014) Grand the elephant has successfully undergone surgery to remove a portion of infected tusk at Tbilisi Zoo in Georgia. British veterinary surgeons used an electric drill to extract the infected piece. (Sept. 18) Video provided by AP
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