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 A new technique isolates neuronal activity during memory consolidation
22.06.2017 | Spanish National Research Council (CSIC)

nachricht CWRU researchers find a chemical solution to shrink digital data storage
22.06.2017 | Case Western Reserve University

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Climate satellite: Tracking methane with robust laser technology

Heatwaves in the Arctic, longer periods of vegetation in Europe, severe floods in West Africa – starting in 2021, scientists want to explore the emissions of the greenhouse gas methane with the German-French satellite MERLIN. This is made possible by a new robust laser system of the Fraunhofer Institute for Laser Technology ILT in Aachen, which achieves unprecedented measurement accuracy.

Methane is primarily the result of the decomposition of organic matter. The gas has a 25 times greater warming potential than carbon dioxide, but is not as...

Im Focus: How protons move through a fuel cell

Hydrogen is regarded as the energy source of the future: It is produced with solar power and can be used to generate heat and electricity in fuel cells. Empa researchers have now succeeded in decoding the movement of hydrogen ions in crystals – a key step towards more efficient energy conversion in the hydrogen industry of tomorrow.

As charge carriers, electrons and ions play the leading role in electrochemical energy storage devices and converters such as batteries and fuel cells. Proton...

Im Focus: A unique data centre for cosmological simulations

Scientists from the Excellence Cluster Universe at the Ludwig-Maximilians-Universität Munich have establised "Cosmowebportal", a unique data centre for cosmological simulations located at the Leibniz Supercomputing Centre (LRZ) of the Bavarian Academy of Sciences. The complete results of a series of large hydrodynamical cosmological simulations are available, with data volumes typically exceeding several hundred terabytes. Scientists worldwide can interactively explore these complex simulations via a web interface and directly access the results.

With current telescopes, scientists can observe our Universe’s galaxies and galaxy clusters and their distribution along an invisible cosmic web. From the...

Im Focus: Scientists develop molecular thermometer for contactless measurement using infrared light

Temperature measurements possible even on the smallest scale / Molecular ruby for use in material sciences, biology, and medicine

Chemists at Johannes Gutenberg University Mainz (JGU) in cooperation with researchers of the German Federal Institute for Materials Research and Testing (BAM)...

Im Focus: Optoelectronic Inline Measurement – Accurate to the Nanometer

Germany counts high-precision manufacturing processes among its advantages as a location. It’s not just the aerospace and automotive industries that require almost waste-free, high-precision manufacturing to provide an efficient way of testing the shape and orientation tolerances of products. Since current inline measurement technology not yet provides the required accuracy, the Fraunhofer Institute for Laser Technology ILT is collaborating with four renowned industry partners in the INSPIRE project to develop inline sensors with a new accuracy class. Funded by the German Federal Ministry of Education and Research (BMBF), the project is scheduled to run until the end of 2019.

New Manufacturing Technologies for New Products

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Plants are networkers

19.06.2017 | Event News

Digital Survival Training for Executives

13.06.2017 | Event News

Global Learning Council Summit 2017

13.06.2017 | Event News

 
Latest News

A new technique isolates neuronal activity during memory consolidation

22.06.2017 | Life Sciences

Plant inspiration could lead to flexible electronics

22.06.2017 | Materials Sciences

A rhodium-based catalyst for making organosilicon using less precious metal

22.06.2017 | Materials Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>