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

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 reproduc e 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.


'"/>

Source:Emory University Health Sciences Center


Related biology news :

1. Scientists ID molecular switch in liver that triggers harmful effects of saturated and trans fats
2. Scientists Replicate Hepatitis C Virus in Laboratory
3. Scientists detect probable genetic cause of some Parkinsons disease cases
4. Scientists find missing enzyme for tuberculosis iron scavenging pathway
5. Scientists seek answers on what activates deadly anthrax spores
6. Yale Scientists Find MicroRNA Regulates Ras Cancer Gene
7. Scientists collaborate to assess health of global environment
8. Scientists decipher genome of fungus that can cause life-threatening infections
9. Scientists discover the cellular roots of graying hair
10. Scientists rid stem cell culture of key animal cells
11. Scientists develop new color-coded test for protein folding
Post Your Comments:
*Name:
*Comment:
*Email:


(Date:3/24/2017)... The Controller General of Immigration from Maldives Mr. Mohamed ... received the prestigious international IAIR Award for the most innovative high security ... ... Maldives Immigration Controller General, ... picture on the right) have received the IAIR award for the "Most ...
(Date:3/23/2017)... Research and Markets has announced the addition of the "Global ... 2025" report to their offering. ... The Global Vehicle Anti-Theft System Market is ... next decade to reach approximately $14.21 billion by 2025. ... all the given segments on global as well as regional levels ...
(Date:3/22/2017)... Calif. , March 21, 2017 ... analytics company serving law enforcement agencies, announced today the ... as director of public safety business development. ... diversified law enforcement experience, including a focus on the ... In his most recent position, Mr. Sheridan served as ...
Breaking Biology News(10 mins):
(Date:8/10/2017)... ... August 09, 2017 , ... SPIE, the ... laboratories — the Wellman Center for Photomedicine, the Manstein Lab in the Cutaneous ... Beckman Laser Institute at University of California, Irvine — and the Hillenkamp family ...
(Date:8/10/2017)... ... August 10, 2017 , ... SPIE, ... Company Ltd. as its exclusive sales representative for SPIE Journals in Japan. Kinokuniya ... SPIE Digital Library in Japan. , “We look forward to expanding our relationship ...
(Date:8/10/2017)... ... August 10, 2017 , ... BellBrook Labs announces the ... , an enabling new high throughput screening (HTS) assay to aid researchers in ... debilitating diseases. , Chemical modification of gene expression, also known as epigenetics, is ...
(Date:8/8/2017)... (PRWEB) , ... August 08, 2017 , ... ... and growth factors expressed in human cells, today announced the launch of ... member of the type I family of interferons that activate Th1-type innate immune responses ...
Breaking Biology Technology: