Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Scientists take aim at virulent bacteria by decoding machinery of key control enzyme

06.05.2005


By deciphering the ingenious mechanism used by a particular enzyme to modify bacterial chromosome chemistry, scientists have come a step closer to designing a new kind of drug that could stop virulent bacterial infections in their tracks. Their research will be published in the May 6 issue of the journal Cell.



Scientists have known for many years that an enzyme called Dam (DNA adenine methyltransferase) plays a role in regulating gene expression in many bacteria. Each time the bacteria reproduce, Dam modifies the A (adenine) nucleotide in the DNA sequence GATC through a chemical reaction known as methylation. Methylation is a biological process used to tag a variety of molecules, including DNA, and is important in cellular processes such as regulating gene expression, DNA replication and repair. In humans DNA methylation occurs on the C (cytosine) rather than the A (adenine) nucleotide.

Recently scientists have discovered a new role for Dam methylation. Dam also is essential for regulating the expression of genes responsible for bacterial virulence. When the gene responsible for Dam is defective, bacteria lose their disease-causing potency. Using the X-ray diffraction facility at the Argonne National Laboratory in Chicago, Xiaodong Cheng, PhD, professor of biochemistry at Emory University School of Medicine and Georgia Research Alliance Eminent Scholar, and John Horton, PhD, Research Assistant Professor, have now solved the co-crystal structure of the Dam enzyme in complex with DNA, which has allowed them to observe exactly how the enzyme finds its target on bacterial DNA.


The Dam enzyme begins by binding non-specifically to DNA, but once it fastens tightly, it glides smoothly down the entire DNA molecule like fingers sliding down a guitar neck searching for the right chord, examining each base pair as it goes. Each time it finds the sequence GATC it stops and methylates the A nucleotide. Dam must move quickly, because if the bacteria reproduce with the wrong methylation pattern, gene expression will be foiled and they will lose their virulence.

"For the first time, using the 3-D crystal structure, we have been able to see the specific Dam structure in action, including the way it binds to the DNA and moves along the base pairs as it recognizes and methylates the A nucleotides," says Dr. Cheng. "Using this information we can potentially design a drug to inhibit this particular enzyme’s chemical reaction or its DNA binding process. This kind of rationally designed drug could be an alternative against infections that are resistant to current antibiotics. And because humans don’t have Dam methylation, this kind of drug would not interfere with important biological processes in humans."

Other coauthors include Dr. Stanley Hattman, professor of biology from University of Rochester, who cloned and sequenced the Dam gene and has been studying the biochemical mechanism of the enzyme and Dr. Albert Jeltsch and his student Kirsten Liebert from International University Bremen in Germany. Dr. Cheng and his colleagues plan to continue their research using structure-based virtual screening techniques and high throughput equipment to screen for potential inhibitor compounds against the Dam enzyme.

Holly Korschun | EurekAlert!
Further information:
http://www.emory.edu

More articles from Life Sciences:

nachricht Cryo-electron microscopy achieves unprecedented resolution using new computational methods
24.03.2017 | DOE/Lawrence Berkeley National Laboratory

nachricht How cheetahs stay fit and healthy
24.03.2017 | Forschungsverbund Berlin e.V.

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Giant Magnetic Fields in the Universe

Astronomers from Bonn and Tautenburg in Thuringia (Germany) used the 100-m radio telescope at Effelsberg to observe several galaxy clusters. At the edges of these large accumulations of dark matter, stellar systems (galaxies), hot gas, and charged particles, they found magnetic fields that are exceptionally ordered over distances of many million light years. This makes them the most extended magnetic fields in the universe known so far.

The results will be published on March 22 in the journal „Astronomy & Astrophysics“.

Galaxy clusters are the largest gravitationally bound structures in the universe. With a typical extent of about 10 million light years, i.e. 100 times the...

Im Focus: Tracing down linear ubiquitination

Researchers at the Goethe University Frankfurt, together with partners from the University of Tübingen in Germany and Queen Mary University as well as Francis Crick Institute from London (UK) have developed a novel technology to decipher the secret ubiquitin code.

Ubiquitin is a small protein that can be linked to other cellular proteins, thereby controlling and modulating their functions. The attachment occurs in many...

Im Focus: Perovskite edges can be tuned for optoelectronic performance

Layered 2D material improves efficiency for solar cells and LEDs

In the eternal search for next generation high-efficiency solar cells and LEDs, scientists at Los Alamos National Laboratory and their partners are creating...

Im Focus: Polymer-coated silicon nanosheets as alternative to graphene: A perfect team for nanoelectronics

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are less stable. Now researchers at the Technical University of Munich (TUM) have, for the first time ever, produced a composite material combining silicon nanosheets and a polymer that is both UV-resistant and easy to process. This brings the scientists a significant step closer to industrial applications like flexible displays and photosensors.

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are...

Im Focus: Researchers Imitate Molecular Crowding in Cells

Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to simulate these confined natural conditions in artificial vesicles for the first time. As reported in the academic journal Small, the results are offering better insight into the development of nanoreactors and artificial organelles.

Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

International Land Use Symposium ILUS 2017: Call for Abstracts and Registration open

20.03.2017 | Event News

CONNECT 2017: International congress on connective tissue

14.03.2017 | Event News

ICTM Conference: Turbine Construction between Big Data and Additive Manufacturing

07.03.2017 | Event News

 
Latest News

Argon is not the 'dope' for metallic hydrogen

24.03.2017 | Materials Sciences

Astronomers find unexpected, dust-obscured star formation in distant galaxy

24.03.2017 | Physics and Astronomy

Gravitational wave kicks monster black hole out of galactic core

24.03.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>