Navigation Links
Iowa State, Ames Lab researchers describe the pump that bacteria use to resist drugs

AMES, Iowa A research team led by Edward Yu of Iowa State University and the Ames Laboratory has identified and described two parts of the three-part system that pumps toxins from bacteria and allows them to resist antibiotics.

The discoveries are published in the Feb. 24 issue of the journal Nature.

The paper describes the co-crystal structure of two parts of the three-part efflux pump that recognizes and removes heavy metal toxins from bacteria. A research team led by Yu an Iowa State associate professor of physics and astronomy, of chemistry, of biochemistry, biophysics and molecular biology and an associate of the U.S. Department of Energy's Ames Laboratory is working to discover the assembled structure of the entire three-part efflux pump.

Yu said a better understanding of how the three parts work together could help medical researchers find ways to restore the effectiveness of antibiotics.

"These pumps have to assemble together in order to pump out heavy metals and antibiotics," Yu said. "Researchers may be able to use these findings to design an inhibitor so the pump can't be assembled and can't work."

Yu and his research team described the first part of the pump the inner membrane transporter known as CusA in the Sept. 23, 2010, issue of the journal Nature.

The current paper describes the inner membrane transporter and how it interacts with the pump's middle adapter, known as CusB. The two parts together are known as the CusBA complex.

The research was supported by grants from the National Institutes of Health. In addition to Yu, the research team includes Robert Jernigan, an Iowa State professor of biochemistry, biophysics and molecular biology and director of Iowa State's Laurence H. Baker Center for Bioinformatics and Biological Statistics; Kanagalaghatta Rajashankar, the operations team leader for the Northeastern Collaborative Access Team facility at Argonne National Laboratory in Argonne, Ill., that's managed by Cornell University in Ithaca, N.Y.; Iowa State post-doctoral researchers Chih-Chia Su and Feng Long; and Iowa State graduate student Michael Zimmermann.

"Determining the structure of CusBA represents a remarkable achievement that has enabled Dr. Yu and his collaborators to model the structure of the entire CusCBA complex," said Jean Chin, who oversees structural biology grants at the National Institutes of Health. "This advance has brought novel insights on how the transporter functions and could lead to ways to block its activity and heighten bacteria's sensitivity to antibiotics."

To make their findings, the researchers purified and co-crystallized the proteins that make up the transporter and adaptor parts of the efflux pump from E. coli bacteria. Then they used X-ray crystallography, including a technique called molecular replacement with single-wavelength anomalous dispersion, to determine the structure and interaction of the two parts.

The studies revealed, molecule by molecule, how the inner transporter's three molecules bind and interact with the middle adaptor's six molecules. The studies also revealed the adaptors' six molecules form a funnel-like channel extending from the top of the transporter.

The researchers used those discoveries to predict how the three-molecule structure of the pump's third part, the outer membrane channel known as CusC, interacts with the CusBA complex.

Yu said discovering the structure of the toxin pump is a significant step toward a better understanding of bacterial resistance to antibiotics.

"A crystallographic model of this tripartite efflux complex has been unavailable," the researchers wrote in a summary of their latest Nature paper, "simply because co-crystallization of different components of the system has proven to be extremely difficult."


Contact: Edward Yu
Iowa State University

Related biology news :

1. New Report Just Published: World Solid-State, Fiber, Gas and Dye Lasers Market Report
2. Iowa State, Ames Lab chemists discover how antiviral drugs bind to and block flu virus
3. Discovery at JGH opens door to new treatments for prostate, brain and skin cancers
4. Iowa State, Ames Lab researchers identify structure that allows bacteria to resist drugs
5. Montana State, partners in 6 states consider converting invasive plants to fuel
6. Iowa State, USDA researchers discover eye test for neurological diseases in livestock
7. Iowa State, Ames Lab researcher develops new way to study single biological molecules
8. AAAS honors Iowa State, Ames Lab researchers for distinguished science
9. NC State researchers get to root of parasite genome
10. Researchers find animal with ability to survive climate change
11. Researchers find an essential gene for forming ears of corn
Post Your Comments:
Related Image:
Iowa State, Ames Lab researchers describe the pump that bacteria use to resist drugs
(Date:6/22/2016)... June 22, 2016 On Monday, the Department ... industry to share solutions for the Biometric Exit Program. ... and Border Protection (CBP), explains that CBP intends to ... the United States , in order ... defeat imposters. Logo - ...
(Date:6/9/2016)... an innovation leader in attendance control systems is proud to announce the introduction of ... make sure the right employees are actually signing in, and to even control the ... ... ... ...
(Date:6/2/2016)... 2016   The Weather Company , an IBM Business ... industry-first capability in which consumers will be able to interact ... questions via voice or text and receive relevant information about ... Marketers have long sought an advertising solution that can ... personal, relevant and valuable; and can scale across millions of ...
Breaking Biology News(10 mins):
(Date:6/27/2016)... ... June 27, 2016 , ... ... Amgen, will join the faculty of the University of North Carolina Kenan-Flagler ... of strategy and entrepreneurship at UNC Kenan-Flagler, with a focus on the school’s ...
(Date:6/24/2016)... NY (PRWEB) , ... June 24, 2016 , ... While ... machines such as the Cary 5000 and the 6000i models are higher end machines ... is the height of the spectrophotometer’s light beam from the bottom of the cuvette ...
(Date:6/23/2016)... 23, 2016 /PRNewswire/ - FACIT has announced the ... biotechnology company, Propellon Therapeutics Inc. ("Propellon" or ... of a portfolio of first-in-class WDR5 inhibitors for ... as WDR5 represent an exciting class of therapies, ... medicine for cancer patients. Substantial advances have been ...
(Date:6/23/2016)... , June, 23, 2016  The Biodesign Challenge ... envision new ways to harness living systems and biotechnology, ... Art (MoMA) in New York City ... 130 participating students, showcased projects at MoMA,s Celeste Bartos ... Paola Antonelli , MoMA,s senior curator of architecture and ...
Breaking Biology Technology: