Featured Research

from universities, journals, and other organizations

Molecule That 'Blocks' Key Bacterial Enzyme May Lead To New Antibiotics

Date:
June 18, 2004
Source:
Rutgers, The State University Of New Jersey
Summary:
Rutgers scientists have deciphered the complex mechanics of microcin J25 (MccJ25), a tiny, natural molecule that acts like a cork in a bottle to block a key bacterial enzyme – potentially leading to a new generation of antibiotics.

NEW BRUNSWICK/PISCATAWAY , N.J. – Rutgers scientists have deciphered the complex mechanics of microcin J25 (MccJ25), a tiny, natural molecule that acts like a cork in a bottle to block a key bacterial enzyme – potentially leading to a new generation of antibiotics.

Related Articles


Two teams of researchers at Rutgers, The State University of New Jersey, discovered independently that MccJ25 uniquely blocks a "tunnel" into the bacterial enzyme, RNA polymerase (RNAP). The "tunnel" is used to bring raw materials for RNA synthesis into the enzyme and to expel byproducts of RNA synthesis.

"Closing the crowded, two-way 'tunnel' starves RNAP, shuts it down and kills the bacteria," said Richard H. Ebright, a Howard Hughes Medical Institute investigator, and a professor in Rutgers' department of chemistry and chemical biology and the Waksman Institute of Microbiology. "Understanding the way in which MccJ25 works sets the stage for the development of novel antibacterial drug designs."

To understand how MccJ25 works, Ebright's group used genetic methods to test hundreds of thousands of RNAP derivatives, or variants, in order to define the binding sites for MccJ25 on RNAP. The researchers also used biophysical methods, attaching fluorescent tags to MccJ25 and to each of a dozen sites in RNAP. Using the tags, the researchers gauged the position of each bound pair in a GPS-like manner, verifying the results of the genetic work. They then used biochemical methods to find out what happened once MccJ25 binds to the RNAP.

The research team of Konstantin Severinov, an associate professor in Rutgers' department of molecular biology and biochemistry and the Waksman Institute, had been the first to demonstrate that RNAP from cells resistant to MccJ25 also showed resistance to the drug in a test tube. In their current work, these researchers used biochemical methods to characterize, in molecular detail, the mechanism of MccJ25 action. In addition, the group used sophisticated biophysical methods that revealed how MccJ25 binds to a single RNAP molecule, stopping it instantaneously.

In the June 18 issue of the journal Molecular Cell, Ebright and colleagues, and Severinov and members of his research team, describe in separate reports how each team used different experimental methods to reach the same conclusions.

"It was only last year that we solved the structure of this molecule, just 21 amino acids long, remarkable both in its size and its structure," said Ebright, a participant in the original structural studies, along with Severinov.

"A great many papers have been published on this molecule in the last year," added Severinov. "Interest in MccJ25 has really exploded."

Shaped like a lasso with its tail pulled back through the loop, MccJ25 is one of very few molecules known to have this highly stable and rigid configuration – a characteristic that may lead to applications beyond drug design.

"MccJ25's sturdy structure permits it to withstand all sorts of harsh environmental conditions," said Severinov. Because of its robustness, he added, "the [U.S.] Department of Defense is interested in the molecule as a potential bacterial decontaminating agent."

MccJ25 inhibits bacterial RNAP and kills bacteria, but it does not inhibit human RNAP and would therefore not kill a human. Ebright cautions, however, that MccJ25 has some shortcomings. It affects only E. coli and closely related bacterial species and is highly subject to developing resistance.

Rutgers researchers are already at work on overcoming these obstacles. Ebright's group has modified the molecule to produce derivatives that have a narrower resistance spectrum. The Severinov group is pursuing the same goal through a National Institutes of Health joint research program with scientists from the University of Tucuman, Argentina, who originally discovered MccJ25 in 1992.


Story Source:

The above story is based on materials provided by Rutgers, The State University Of New Jersey. Note: Materials may be edited for content and length.


Cite This Page:

Rutgers, The State University Of New Jersey. "Molecule That 'Blocks' Key Bacterial Enzyme May Lead To New Antibiotics." ScienceDaily. ScienceDaily, 18 June 2004. <www.sciencedaily.com/releases/2004/06/040618070302.htm>.
Rutgers, The State University Of New Jersey. (2004, June 18). Molecule That 'Blocks' Key Bacterial Enzyme May Lead To New Antibiotics. ScienceDaily. Retrieved December 22, 2014 from www.sciencedaily.com/releases/2004/06/040618070302.htm
Rutgers, The State University Of New Jersey. "Molecule That 'Blocks' Key Bacterial Enzyme May Lead To New Antibiotics." ScienceDaily. www.sciencedaily.com/releases/2004/06/040618070302.htm (accessed December 22, 2014).

Share This


More From ScienceDaily



More Matter & Energy News

Monday, December 22, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Will New A350 Help Airbus Fly?

Will New A350 Help Airbus Fly?

Reuters - Business Video Online (Dec. 22, 2014) Qatar Airways takes first delivery of Airbus' new A350 passenger jet. As Joel Flynn reports it's the planemaker's response to the Boeing 787 Dreamliner and the culmination of eight years of development. Video provided by Reuters
Powered by NewsLook.com
Man Parachutes Off Lawn Chair Airlifted By Helium Balloons

Man Parachutes Off Lawn Chair Airlifted By Helium Balloons

Buzz60 (Dec. 22, 2014) A BASE jumper rides a lawn chair, a shotgun, and a giant bunch of helium balloons into the sky in what seems like a country version of the movie 'Up." Jen Markham has the story. Video provided by Buzz60
Powered by NewsLook.com
Touch-Free Smart Phone Empowers Mobility-Impaired

Touch-Free Smart Phone Empowers Mobility-Impaired

Reuters - Innovations Video Online (Dec. 21, 2014) A touch-free phone developed in Israel enables the mobility-impaired to operate smart phones with just a movement of the head. Suzannah Butcher reports. Video provided by Reuters
Powered by NewsLook.com
Existing Chemical Compounds Could Revive Failing Antibiotics, Says Danish Scientist

Existing Chemical Compounds Could Revive Failing Antibiotics, Says Danish Scientist

Reuters - Innovations Video Online (Dec. 21, 2014) A team of scientists led by Danish chemist Jorn Christensen says they have isolated two chemical compounds within an existing antipsychotic medication that could be used to help a range of failing antibiotics work against killer bacterial infections, such as Tuberculosis. Jim Drury went to meet him. 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


Space & Time

Matter & Energy

Computers & Math

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