Researchers image crucial anthrax protein

Jul 14, 2009
Crystal structure of the anthrax protein CapD.

(PhysOrg.com) -- Anthrax, long feared for its potential as a biological weapon, has lost some of its mystery. Researchers at the U.S. Department of Energy's (DOE) Argonne National Laboratory, in collaboration with scientists at the University of Chicago, have determined the structure of a protein crucial to the virulence of anthrax bacteria.

One of anthrax’s most dangerous features is its ability to exist as a spore—an inactive sealed package that can survive extreme conditions outside its host for long periods. Once in the bloodstream, however, the bacterium germinates, triggering a dangerous infection. The activated anthrax bacterium looks like a thin rod swathed in a thick protective capsule coating. This capsule coat lets the bacteria evade macrophages, the roving that form the first line of our immune response.

The researchers examined a gene that codes for a particular enzyme called CapD, a protein that helps the bacteria form its protective coating once it enters the body. CapD sits on the surface of the cell, grabs molecules of the capsule’s building blocks (poly-D-gamma-glutamic acid, or PDGA) and attaches them to the bacteria’s outer wall to form its shield.

“The PDGA peptide construction is unusual; for example, it is made with the ‘D’ of glutamic acid instead of the ‘L’ form found in proteins,” said Andrzej Joachimiak, a co-author of the study. “This is why macrophages can’t deal with the protective capsule of anthrax. They could easily find a regular peptide made of ‘L’ amino acids, but this is a unique configuration, and they can’t recognize it. That’s how they fool the system.”

Joachimiak and the team wanted to map out the crystal structure of CapD. Once the researchers discovered the enzyme's structure, they could begin to search for a molecule that could block its function—which in turn would make the bacteria more vulnerable to human defenses.

By using brilliant X-rays at the Structural Biology Center 19ID beamline at Argonne's Advanced Photon Source, the team was able to image two versions of the protein: one with a molecule of imitation capsule material attached, and one without.

“It looks like Pac-Man,” Joachimiak said. “The jaws are open when it’s empty, but when the ligand attaches, it clamps down around it.” Then the enzyme cleaves the polymer and attaches it to the surface of the cell.

The paper, “Crystal Structure of Bacillus anthracis Transpeptidase Enzyme CapD”, will be published in the Journal of Biological Chemistry.

The work to characterize anthrax and other pathogenic or important bacteria is part of an initiative by the Midwest Center for Structural Genomics, an NIH-funded consortium of eight institutions, and the Region V Great Lakes Regional Center of Excellence in Biodefense and Emerging Infectious Diseases Consortium.

Provided by Argonne National Laboratory (news : web)

Explore further: Dead feeder cells support stem cell growth

Related Stories

Structural study of anthrax yields new antibiotic target

Jan 28, 2008

Researchers studying anthrax knew they were onto something when they discovered an opponent the bacterium couldn’t outwit. Probing a bit deeper, they discovered this was because the attacker was interacting ...

Team IDs weakness in anthrax bacteria

Jan 23, 2008

MIT and New York University researchers have identified a weakness in the defenses of the anthrax bacterium that could be exploited to produce new antibiotics.

Anthrax cellular entry point uncovered

Jan 25, 2008

The long-sought-after biological “gateway” that anthrax uses to enter healthy cells has been uncovered by microbiologists at the University of Alabama at Birmingham (UAB).

Anthrax Detector Developed

Aug 16, 2006

Spores of the dreaded Bacillus anthracis have already been used as a bioweapon against the civilian population. Once inhaled, the anthrax pathogen almost always leads to death if the victims are not treated within 24 to 48 ...

Recommended for you

Dead feeder cells support stem cell growth

Apr 24, 2015

Stem cells naturally cling to feeder cells as they grow in petri dishes. Scientists have thought for years that this attachment occurs because feeder cells serve as a support system, providing stems cells ...

Improving accuracy in genome editing

Apr 23, 2015

Imagine a day when scientists are able to alter the DNA of organisms in the lab in the search for answers to a host of questions. Or imagine a day when doctors treat genetic disorders by administering drugs ...

Drug research enhanced by fragment screening libraries

Apr 22, 2015

Generation of fragment screening libraries could enhance the analysis and application of natural products for medicinal chemistry and drug discovery, according to Griffith University's Professor Ronald Quinn.

Decoding the cell's genetic filing system

Apr 22, 2015

A fully extended strand of human DNA measures about five feet in length. Yet it occupies a space just one-tenth of a cell by wrapping itself around histones—spool-like proteins—to form a dense hub of ...

User comments : 0

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.