Featured Research

from universities, journals, and other organizations

In Mapping The Structure Of Short-Lived Bacterial "Switches," Biochemist May Find Novel Answer To Antibiotic Resistance

Date:
December 24, 1999
Source:
Brandeis University
Summary:
Atom by atom, a Brandeis University researcher and her colleagues have unmasked the structure of ephemeral protein "switches" that play a critical role in transforming mild-mannered bacteria into lethal parasites. The finding, reported in the Dec. 23 issue of the journal Nature, raises the prospect of a novel kind of antibiotic to fill the void left by growing resistance among many bacteria to traditional drugs.

WALTHAM, Mass. -- Atom by atom, a Brandeis University researcher and her colleagues have unmasked the structure of ephemeral protein "switches" that play a critical role in transforming mild-mannered bacteria into lethal parasites. The finding, reported in the Dec. 23 issue of the journal Nature, raises the prospect of a novel kind of antibiotic to fill the void left by growing resistance among many bacteria to traditional drugs.

The research, led by Brandeis biochemist Dorothee Kern, also involved scientists from the University of Wisconsin, Lawrence Berkeley National Laboratory, and the University of California at Berkeley.

Current-generation antibiotics, which kill off normal strains of bacteria while leaving resistant ones unaffected, essentially select for the survival of resistant strains, sometimes inducing resistance in as little as six months. The protein family Kern describes in the Nature paper represents a potential target for a whole new class of antibiotics to specifically prevent pathogenic bacteria from becoming virulent and attacking the body's cells.

"Most conventional antibiotics work by inhibiting processes essential to cell viability, such as DNA translation or the assembly of cell membranes," says Kern, an assistant professor of biochemistry at Brandeis. "Few attempts have been made to target the mechanisms by which pathogenic bacteria become virulent and infect host cells."

Part of a two-component system that dominates signal transduction in bacteria, the phosphate-juggling protein switch mapped out by Kern and her colleagues works by snatching a single phosphate ion from the amino acid histidine. The phosphorylated protein then binds to bacterial DNA, turning on genes such as those that instigate infection. These protein switches are ubiquitous in bacteria, but aren't found in humans -- making them an ideal target for antibiotics.

The protein switch studied by Kern is part of a common two-component system wherein a biological signal prompts a histidine molecule on one component to transfer a phosphate ion to an aspartate molecule on a second component. A strikingly similar two-component mechanism operates among many species of bacteria. "Our goal was to unravel the structural basis of the switch in the signal cascade at atomic resolution, with the hopes of developing new approaches for treating multiple-resistant infections," Kern says.

It's the first time the structure of such a short-lived protein has ever been pinpointed by scientists, Kern says, and heralds new possibilities for future NMR imaging of other evanescent biomolecules.

Key to the research was an innovative approach to nuclear magnetic resonance (NMR) spectroscopy that allowed Kern to regenerate, for a day and a half, the fleeting active configuration the protein switch normally assumes only during the few minutes when it grabs and holds a phosphate ion. The rapid loss of these ions -- necessary for fast responses to the environment -- usually makes the active, phosphate-bound form of the switch far too transient for structural analysis. To keep the protein switch in its active state long enough to get a good snapshot, Kern collected NMR spectra on the protein during catalysis using a constant stream of phosphate.

Kern's co-authors on the paper are Brian F. Volkman of the University of Wisconsin, Sydney Kustu of the University of California at Berkeley, and Peter Luginbόhl, Michael J. Nohaile, and David E. Wemmer of the Lawrence Berkeley National Laboratory. The research was sponsored by the U.S. Department of Energy and the National Science Foundation.


Story Source:

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


Cite This Page:

Brandeis University. "In Mapping The Structure Of Short-Lived Bacterial "Switches," Biochemist May Find Novel Answer To Antibiotic Resistance." ScienceDaily. ScienceDaily, 24 December 1999. <www.sciencedaily.com/releases/1999/12/991224090906.htm>.
Brandeis University. (1999, December 24). In Mapping The Structure Of Short-Lived Bacterial "Switches," Biochemist May Find Novel Answer To Antibiotic Resistance. ScienceDaily. Retrieved October 21, 2014 from www.sciencedaily.com/releases/1999/12/991224090906.htm
Brandeis University. "In Mapping The Structure Of Short-Lived Bacterial "Switches," Biochemist May Find Novel Answer To Antibiotic Resistance." ScienceDaily. www.sciencedaily.com/releases/1999/12/991224090906.htm (accessed October 21, 2014).

Share This



More Plants & Animals News

Tuesday, October 21, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

White Lion Cubs Born in Belgrade Zoo

White Lion Cubs Born in Belgrade Zoo

AFP (Oct. 20, 2014) — Two white lion cubs, an extremely rare subspecies of the African lion, were recently born at Belgrade Zoo. They are being bottle fed by zoo keepers after they were rejected by their mother after birth. Duration: 00:42 Video provided by AFP
Powered by NewsLook.com
Traditional Farming Methods Gaining Ground in Mali

Traditional Farming Methods Gaining Ground in Mali

AFP (Oct. 20, 2014) — He is leading a one man agricultural revolution in Mali - Oumar Diatabe uses traditional farming methods to get the most out of his land and is teaching others across the country how to do the same. Duration: 01:44 Video provided by AFP
Powered by NewsLook.com
Goliath Spider Will Give You Nightmares

Goliath Spider Will Give You Nightmares

Buzz60 (Oct. 20, 2014) — An entomologist stumbled upon a South American Goliath Birdeater. With a name like that, you know it's a terrifying creepy crawler. Sean Dowling (@SeanDowlingTV) has the details. Video provided by Buzz60
Powered by NewsLook.com
Adorable Video of Baby Rhino and Lamb Friend Playing

Adorable Video of Baby Rhino and Lamb Friend Playing

Buzz60 (Oct. 20, 2014) — Gertjie the Rhino and Lammie the Lamb are teaching the world about animal conservation and friendship. TC Newman (@PurpleTCNewman) has the adorable video! Video provided by Buzz60
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