Navigation Links
Study: Odd biochemistry yields lethal bacterial protein
Date:1/22/2013

CHAMPAIGN, Ill. While working out the structure of a cell-killing protein produced by some strains of the bacterium Enterococcus faecalis, researchers stumbled on a bit of unusual biochemistry. They found that a single enzyme helps form distinctly different, three-dimensional ring structures in the protein, one of which had never been observed before.

The new findings, reported in Nature Chemical Biology, should help scientists find new ways to target the enterococcal cytolysin protein, a "virulence factor that is associated with acute infection in humans," said University of Illinois chemistry and Institute for Genomic Biology professor Wilfred van der Donk, who conducted the study with graduate student Weixin Tang.

Enterococcus faecalis (EN-ter-oh-cock-us faye-KAY-liss) is a normal microbial inhabitant of the gastrointestinal tracts of humans and other mammals and generally does not harm its host. Some virulent strains, however, produce cytolysin (sigh-toe-LIE-sin), a protein that, once assembled, attacks other microbes and kills mammalian cells.

"The cytolysin protein made by Enterococcus faecalis consists of two compounds that have no activity by themselves but when combined kill human cells," van der Donk said. "We know from epidemiological studies that if you are infected with a strain of E. faecalis that has the genes to make cytolysin, you have a significantly higher chance of dying from your infection." E. faecalis contributes to root canal infections, urinary tract infections, endocarditis, meningitis, bacteremia and other infections.

Enterococcal cytolysin belongs to a class of antibiotic proteins, called lantibiotics, which have two or more sulfur-containing ring structures. Scientists had been unable to determine the three-dimensional structure of this cytolysin because the bacterium produces it at very low concentrations. Another problem that has stymied researchers is that the two protein components of cytolysin tend to clump together when put in a lab dish.

Van der Donk and Tang got around these problems by producing the two cytolysin components separately in another bacterium, Escherichia coli (esh-uh-REE-kee-uh KOH-lie), and analyzing them separately.

"The two components are both cyclic peptides, one with three rings and the other with two rings," van der Donk said. "Curiously, a single enzyme makes both compounds."

In a series of experiments, the researchers found that one ring on each of the proteins adopted a (D-L) stereochemistry that is common in lantibiotics (see image, above). But the other rings all had an unusual (L-L) configuration, something van der Donk had never seen before.

Scientists had assumed that the enzyme that shaped enterococcal cytolysin, a lantibiotic synthetase, acted like a three-dimensional mold that gave the ring structures of cytolysin the exact same stereochemistry, van der Donk said.

"But we found that the enzyme, enterococcal cytolysin synthetase, makes the rings with different stereochemistry," he said. "I don't know of any other examples where one enzyme can make very similar products but with different stereochemistries."

The researchers don't know how the enzyme accomplishes this feat, but found a clue in the sequence of amino acids that make up the protein rings. The chemical characteristics of the three amino acids in the middle of the ring structure and their proximity to another amino acid, a cysteine, determined whether the rings took on a D-L or L-L stereochemistry.

The researchers tested the idea that the amino acid sequence of the cytolysin protein was guiding the stereochemistry by looking at other lantibiotic proteins with similar sequences. So far, every protein they've tested that has the same sequence characteristics conforms to the pattern they discovered, van der Donk said.

Further tests showed that the cytolysin produced in E. coli had the same anti-microbial and cell-killing potency as the E. faecalis variety.

"Knowing the structure of enterococcal cytolysin and having a method to produce it in relatively large quantities will allow scientists to find out how it kills human cells and, in turn, how we might fight against it," van der Donk said.


'/>"/>

Contact: Diana Yates
diya@illinois.edu
217-333-5802
University of Illinois at Urbana-Champaign
Source:Eurekalert  

Related biology news :

1. BYU study: Using a gun in bear encounters doesnt make you safer
2. 15-year study: When it comes to creating wetlands, Mother Nature is in charge
3. Study: Exercise can lead to female orgasm, sexual pleasure
4. U of I study: Lose body weight before gaining baby weight
5. Study: Men who do load-bearing exercise in early 20s may be shielded from osteoporosis
6. USF study: Common fungicide wreaks havoc on freshwater ecosystems
7. Army study: DNA vaccine and duck eggs protect against hantavirus disease
8. Study: In-patient, out-patient stroke rehab might benefit from yoga
9. Study: Seeking Arctic methane has serious implications for Florida coastline
10. Study: Seeping Arctic methane has serious implications for Florida coastline
11. Study: No-fat, low-fat dressings dont get most nutrients out of salads
Post Your Comments:
*Name:
*Comment:
*Email:
Related Image:
Study: Odd biochemistry yields lethal bacterial protein
(Date:3/22/2016)... , PROVO and ... Newborn Screening Ontario (NSO), which operates the highest sample ... molecular testing, and Tute Genomics and UNIConnect, leaders in ... respectively, today announced the launch of a project to ... (NGS) testing panel. NSO has been ...
(Date:3/18/2016)... 18, 2016 --> ... ICT, Manned & Unmanned Vehicles, Physical infrastructure and Perimeter Surveillance ... in the border security market and the continuing migration crisis ... Europe has led visiongain to publish this ... --> defence & security companies in the ...
(Date:3/15/2016)... , March 15, 2016 ... report published by Transparency Market Research "Digital Door Lock Systems ... Forecast 2015 - 2023," the global digital door lock systems ... Mn in 2014 and is forecast to grow at a ... of micro, small and medium enterprises (MSMEs) across the world ...
Breaking Biology News(10 mins):
(Date:4/27/2016)... ... April 27, 2016 , ... Cambridge Semantics, ... web technology, today announced that it has been named to The Silicon Review’s “20 ... services and other markets, Cambridge Semantics serves the needs of end users facing some ...
(Date:4/27/2016)... SPRING, Md. and RESEARCH TRIANGLE ... Therapeutics Corporation (NASDAQ: UTHR ) announced today ... Executive Officer, of United Therapeutics will provide an overview ... Bank 41 st Annual Health Care Conference. ... 5, 2016, at 10:00 a.m. Eastern Time, and can ...
(Date:4/27/2016)... ... , ... Global Stem Cells Group CEO Benito Novas announced that ... GSCG affiliate Kimera Labs in Miami. , In 2004, Ross received his Ph.D. in ... hematologic disorders and the suppression of graft vs. host disease (GVHD) under UM Professor ...
(Date:4/26/2016)... ... April 26, 2016 , ... ... Arianpour has joined the company as Chief Business Officer. Arianpour, a genomics pioneer ... technologies to market, was most recently Chief Commercial Officer of Pathway Genomics. He ...
Breaking Biology Technology: