Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

DNA repair protein caught in act of molecular theft

11.11.2010
Scientists have observed, for the first time, an intermediate stage in the chemical process that repairs DNA methylation damage and regulates many important biological functions that impact health conditions such as obesity, cancer and diabetes.

The observations focused on the bacterial DNA repair protein AlkB, but the results also apply to several proteins in the same family that play key regulatory roles in humans. Armed with these results, researchers may one day develop methods for blocking the protein's efforts to perform the biologically important demethylation function in human cells, said Chuan He, Professor in Chemistry at the University of Chicago.

"This family of proteins is the most exciting protein family now in biology," said He, who led the study. "These proteins directly impact obesity, cancer and diabetes, and they do not go through the traditional pathways of DNA or protein modification. Most likely they go through RNA modification and demodification. It's a new area of biological research."

He and his colleagues at UChicago and the University of Wisconsin-Madison report their findings in the journal Nature, published online on Nov. 10.

The Nature article presents new details about how proteins chemically alter biological molecules and their functioning via a process called oxidative demethylation. Methylation is a chemical process that helps control how DNA and other proteins carry out their functions in the body. In the case of DNA, methylation and demethylation affect how the genetic code gets made into proteins. In recent years scientists had assumed that AlkB and related proteins initiate an oxidizing reaction to remove a hydrocarbon group (the methyls) from the group's host molecule.

"Biological methylation is one of the most important processes in nature to regulate all kinds of things," He said, including how cells differentiate into their final state and how genetic information is transmitted to proteins.

The UChicago researchers recently invented a chemical technique to trap the AlkB protein when it reacts with its host molecule — a previously unobserved, ephemeral process. The technique tethers the protein to the host molecule. "It's stuck there. It can react and stop at the intermediate stage," He said.

Bizarre Observation

Two of the enzymatic intermediates that He's team trapped and observed were predicted and expected based on the chemical principles involved, but these fleeting species were directly observed for the first time. For a third intermediate, however, "we observed something bizarre," He said.

Researchers at UW-Madison then carried out computational calculations on the electronic and structural properties of the intermediates that He observed in his experiments. The calculations showed that the bizarrely behaving intermediate was "zwitterionic," meaning that it carried an overall neutral charge, but displayed positive or negative charges when interacting with different atoms.

"We were able to show that the intermediate captured by Chuan's beautiful experiment is zwitterionic in nature, which offers new clues regarding the chemical steps of the biological demethylation process," said Qiang Cui, professor of chemistry at UW-Madison.

The team documented the role of oxidation in demethylation using the U.S. Department of Energy's Advanced Photon Source at Argonne National Laboratory. The APS produces the brightest X-rays in the Western Hemisphere, which permitted the team to determine the crystal structures that show the three-dimensional atomic framework of the intermediate stage in the demethylation process.

Members of He's research team visit the APS two or three times a month for a full day of experimentation. "We literally collected close to a hundred data sets there," He said. The researchers take multiple data sets at different intervals to confirm the accuracy of their results.

The National Institutes of Health supported this study.

Steve Koppes | EurekAlert!
Further information:
http://www.uchicago.edu

More articles from Life Sciences:

nachricht Hunting pathogens at full force
22.03.2017 | Helmholtz-Zentrum für Infektionsforschung

nachricht A 155 carat diamond with 92 mm diameter
22.03.2017 | Universität Augsburg

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

Pulverizing electronic waste is green, clean -- and cold

22.03.2017 | Materials Sciences

Astronomers hazard a ride in a 'drifting carousel' to understand pulsating stars

22.03.2017 | Physics and Astronomy

New gel-like coating beefs up the performance of lithium-sulfur batteries

22.03.2017 | Materials Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>