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RUB researchers clarify catalysis mechanism of cell growth protein Ras
Date:9/18/2012

Proteins accelerate certain chemical reactions in cells by several orders of magnitude. The molecular mechanism by which the Ras protein accelerates the cleavage of the molecule GTP and thus slows cell growth is described by biophysicists at the Ruhr-Universitt Bochum led by Prof. Dr. Klaus Gerwert in the Online Early Edition of the journal PNAS. Using a combination of infrared spectroscopy and computer simulations, they showed that Ras puts a phosphate chain under tension to such an extent that a phosphate group can very easily detach - the brake for cell growth. Mutated Ras is involved in tumour formation, because this reaction slows down and the brake for cell growth fails. "Our findings could help to develop small molecules that restore the Ras proteins to the right speed", says Prof. Gerwert. "Such molecules would then be interesting for molecular cancer therapy."

On/off: the Ras code

The Ras protein switches the cell growth off by detaching a phosphate group from the small bound guanosine triphosphate, GTP for short. GTP has three interlinked phosphate groups. If it is present in water, the third phosphate group can split off spontaneously - even without the help of the protein Ras. This process is very slow though. Ras accelerates the splitting by a magnitude of five, a second protein, called GAP, by a further magnitude of five. What causes this acceleration has now been found out by the Bochum team.

How Ras spans the phosphate chain

Ras brings the chain of three phosphate groups at the GTP into a certain shape. It turns the third and second phosphate group to each other so that the chain is tensioned. "Like winding up a spring in a toy car by turning a screw", explains Prof. Gerwert. "Ras is the screw, the phosphate groups form the spring." The protein GAP tensions the spring further by also turning the first phosphate group against the second. In this way, the GTP gets into such a high-energy s
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Contact: Prof. Dr. Klaus Gerwert
klaus.gerwert@bph.ruhr-uni-bochum.de
49-234-322-4461
Ruhr-University Bochum
Source:Eurekalert

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