Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

New study may shed light on protein-drug interactions

17.01.2008
Proteins, the biological molecules that are involved in virtually every action of every organism, may themselves move in surprising ways, according to a recent study from the U.S. Department of Energy's Argonne National Laboratory that may shed new light on how proteins interact with drugs and other small molecules.

This study, which relied on the intense X-ray beams available at Argonne's Advanced Photon Source, uses a new approach to characterize the ways in which proteins move around in solution to interact with other molecules, including drugs, metabolites or pieces of DNA.

"Proteins are not static, they're dynamic," said Argonne biochemist Lee Makowski, who headed the project. "Part of the common conception of proteins as rigid bodies comes from the fact that we know huge amounts about protein structures but much less about how they move."

The study of proteins had long focused almost exclusively on their structures, parts of which can resemble chains, sheets or helices. To determine these, scientists use high-energy X-rays to take snapshots of proteins frozen in a single conformation within a highly ordered crystal. However, biologists had made relatively little progress in using these pictures to show how proteins can reconfigure themselves in different environments.

While scientists had expected proteins to behave similarly in regions of high and low protein concentration – from as high as 30 percent protein to less than 1 percent protein, respectively – they instead found that proteins had a much larger range of motion and could contort themselves into many more configurations in the dilute solutions. "The difference is comparable to skipping through an open field or being crammed into a crowded elevator," Makowski said.

For more than a century, the standard model of protein behavior depicted them as inflexible "locks" that could interact only with a small set of equally rigid molecular "keys." Even today's introductory biology courses rely on descriptions of protein behavior that require them to swivel and pivot very little as they interact with other biological molecules, according to Makowski. "That's a very powerful image but it's not the whole story," he said. "We've learned that proteins in solution can take on an entire ensemble of slightly different structures and that, for most proteins, this ensemble grows much larger as you go to lower and lower concentrations."

Makowski and his colleagues were also surprised to discover that environmental conditions strongly influence which state in this "ensemble" of conformations a protein prefers to enter. Most of a protein's common configurations have a functional purpose, he said, as it is "not likely to twist itself into something completely irrelevant to its function."

For example, one of the five proteins examined in the study, hemoglobin, has two favored conformations: one in which it binds oxygen very readily and one in which it does not. When hemoglobin is placed in a solution that contains a great deal of available oxygen, it spends most of the time in the former state, but when oxygen is not easily accessible, it usually flips into the latter. "We now know that in dilute solutions, hemoglobin can actually take on both conformations — even in the absence of oxygen," he added.

By keeping all of the environmental factors the same save for the protein concentration in the solution, Makowski and his team discovered another surprising result. Scientists had known for many years that when proteins are too concentrated, they aggregate and fall out of solution. However, biochemists previously had difficulty explaining why a similar effect also occurs in overly dilute solutions.

Proteins have hydrophobic – or "water-hating" – core regions that try to avoid touching water if at all possible. Because of this characteristic, proteins will rearrange themselves to protect these regions from coming into contact with water. In dilute solutions, however, Makowski's team discovered that proteins fluctuate far more than in concentrated solutions, and these fluctuations expose the proteins' hydrophobic core, making them more likely to stick to one another or to the container walls.

The results of the research appear in the January 11 issue of the Journal of Molecular Biology.

Argonne National Laboratory, a renowned R&D center, brings the world's brightest scientists and engineers together to find exciting and creative new solutions to pressing national problems in science and technology. The nation's first national laboratory, Argonne conducts leading-edge basic and applied scientific research in virtually every scientific discipline. Argonne researchers work closely with researchers from hundreds of companies, universities, and federal, state and municipal agencies to help them solve their specific problems, advance America 's scientific leadership and prepare the nation for a better future. With employees from more than 60 nations, Argonne is managed by UChicago Argonne, LLC for the U.S. Department of Energy's Office of Science.

Steve McGregor | EurekAlert!
Further information:
http://www.anl.gov

More articles from Studies and Analyses:

nachricht The personality factor: How to foster the sharing of research data
06.09.2017 | ZBW – Leibniz-Informationszentrum Wirtschaft

nachricht Europe’s Demographic Future. Where the Regions Are Heading after a Decade of Crises
10.08.2017 | Berlin-Institut für Bevölkerung und Entwicklung

All articles from Studies and Analyses >>>

The most recent press releases about innovation >>>

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

Im Focus: LaserTAB: More efficient and precise contacts thanks to human-robot collaboration

At the productronica trade fair in Munich this November, the Fraunhofer Institute for Laser Technology ILT will be presenting Laser-Based Tape-Automated Bonding, LaserTAB for short. The experts from Aachen will be demonstrating how new battery cells and power electronics can be micro-welded more efficiently and precisely than ever before thanks to new optics and robot support.

Fraunhofer ILT from Aachen relies on a clever combination of robotics and a laser scanner with new optics as well as process monitoring, which it has developed...

Im Focus: The pyrenoid is a carbon-fixing liquid droplet

Plants and algae use the enzyme Rubisco to fix carbon dioxide, removing it from the atmosphere and converting it into biomass. Algae have figured out a way to increase the efficiency of carbon fixation. They gather most of their Rubisco into a ball-shaped microcompartment called the pyrenoid, which they flood with a high local concentration of carbon dioxide. A team of scientists at Princeton University, the Carnegie Institution for Science, Stanford University and the Max Plank Institute of Biochemistry have unravelled the mysteries of how the pyrenoid is assembled. These insights can help to engineer crops that remove more carbon dioxide from the atmosphere while producing more food.

A warming planet

Im Focus: Highly precise wiring in the Cerebral Cortex

Our brains house extremely complex neuronal circuits, whose detailed structures are still largely unknown. This is especially true for the so-called cerebral cortex of mammals, where among other things vision, thoughts or spatial orientation are being computed. Here the rules by which nerve cells are connected to each other are only partly understood. A team of scientists around Moritz Helmstaedter at the Frankfiurt Max Planck Institute for Brain Research and Helene Schmidt (Humboldt University in Berlin) have now discovered a surprisingly precise nerve cell connectivity pattern in the part of the cerebral cortex that is responsible for orienting the individual animal or human in space.

The researchers report online in Nature (Schmidt et al., 2017. Axonal synapse sorting in medial entorhinal cortex, DOI: 10.1038/nature24005) that synapses in...

Im Focus: Tiny lasers from a gallery of whispers

New technique promises tunable laser devices

Whispering gallery mode (WGM) resonators are used to make tiny micro-lasers, sensors, switches, routers and other devices. These tiny structures rely on a...

Im Focus: Ultrafast snapshots of relaxing electrons in solids

Using ultrafast flashes of laser and x-ray radiation, scientists at the Max Planck Institute of Quantum Optics (Garching, Germany) took snapshots of the briefest electron motion inside a solid material to date. The electron motion lasted only 750 billionths of the billionth of a second before it fainted, setting a new record of human capability to capture ultrafast processes inside solids!

When x-rays shine onto solid materials or large molecules, an electron is pushed away from its original place near the nucleus of the atom, leaving a hole...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

“Lasers in Composites Symposium” in Aachen – from Science to Application

19.09.2017 | Event News

I-ESA 2018 – Call for Papers

12.09.2017 | Event News

EMBO at Basel Life, a new conference on current and emerging life science research

06.09.2017 | Event News

 
Latest News

Fraunhofer ISE Pushes World Record for Multicrystalline Silicon Solar Cells to 22.3 Percent

25.09.2017 | Power and Electrical Engineering

Usher syndrome: Gene therapy restores hearing and balance

25.09.2017 | Health and Medicine

An international team of physicists a coherent amplification effect in laser excited dielectrics

25.09.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>