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 Nanoparticle Exposure Can Awaken Dormant Viruses in the Lungs
16.01.2017 | Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt

nachricht Cholera bacteria infect more effectively with a simple twist of shape
13.01.2017 | Princeton 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: Interfacial Superconductivity: Magnetic and superconducting order revealed simultaneously

Researchers from the University of Hamburg in Germany, in collaboration with colleagues from the University of Aarhus in Denmark, have synthesized a new superconducting material by growing a few layers of an antiferromagnetic transition-metal chalcogenide on a bismuth-based topological insulator, both being non-superconducting materials.

While superconductivity and magnetism are generally believed to be mutually exclusive, surprisingly, in this new material, superconducting correlations...

Im Focus: Studying fundamental particles in materials

Laser-driving of semimetals allows creating novel quasiparticle states within condensed matter systems and switching between different states on ultrafast time scales

Studying properties of fundamental particles in condensed matter systems is a promising approach to quantum field theory. Quasiparticles offer the opportunity...

Im Focus: Designing Architecture with Solar Building Envelopes

Among the general public, solar thermal energy is currently associated with dark blue, rectangular collectors on building roofs. Technologies are needed for aesthetically high quality architecture which offer the architect more room for manoeuvre when it comes to low- and plus-energy buildings. With the “ArKol” project, researchers at Fraunhofer ISE together with partners are currently developing two façade collectors for solar thermal energy generation, which permit a high degree of design flexibility: a strip collector for opaque façade sections and a solar thermal blind for transparent sections. The current state of the two developments will be presented at the BAU 2017 trade fair.

As part of the “ArKol – development of architecturally highly integrated façade collectors with heat pipes” project, Fraunhofer ISE together with its partners...

Im Focus: How to inflate a hardened concrete shell with a weight of 80 t

At TU Wien, an alternative for resource intensive formwork for the construction of concrete domes was developed. It is now used in a test dome for the Austrian Federal Railways Infrastructure (ÖBB Infrastruktur).

Concrete shells are efficient structures, but not very resource efficient. The formwork for the construction of concrete domes alone requires a high amount of...

Im Focus: Bacterial Pac Man molecule snaps at sugar

Many pathogens use certain sugar compounds from their host to help conceal themselves against the immune system. Scientists at the University of Bonn have now, in cooperation with researchers at the University of York in the United Kingdom, analyzed the dynamics of a bacterial molecule that is involved in this process. They demonstrate that the protein grabs onto the sugar molecule with a Pac Man-like chewing motion and holds it until it can be used. Their results could help design therapeutics that could make the protein poorer at grabbing and holding and hence compromise the pathogen in the host. The study has now been published in “Biophysical Journal”.

The cells of the mouth, nose and intestinal mucosa produce large quantities of a chemical called sialic acid. Many bacteria possess a special transport system...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

12V, 48V, high-voltage – trends in E/E automotive architecture

10.01.2017 | Event News

2nd Conference on Non-Textual Information on 10 and 11 May 2017 in Hannover

09.01.2017 | Event News

Nothing will happen without batteries making it happen!

05.01.2017 | Event News

 
Latest News

Water - as the underlying driver of the Earth’s carbon cycle

17.01.2017 | Earth Sciences

Interfacial Superconductivity: Magnetic and superconducting order revealed simultaneously

17.01.2017 | Materials Sciences

Smart homes will “LISTEN” to your voice

17.01.2017 | Architecture and Construction

VideoLinks
B2B-VideoLinks
More VideoLinks >>>