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Big stride in understanding PP1, the ubiquitous enzyme
Date:3/3/2014

PROVIDENCE, R.I. [Brown University] In the Proceedings of the National Academy of Sciences, a team of scientists at Brown University reports a major step forward in determining the specific behavior of the ubiquitous enzyme PP1 implicated in a wide range of diseases including cancer.

PP1, whose role is to enable the passage of molecular messages among cells, is found pretty much everywhere in the body. Its wide range of responsibilities means it is essential to many healthy functions and, when things go wrong, to diseases. But its very versatility has prevented it from being a target for drug development, said Rebecca Page, associate professor of biology at Brown and the paper's corresponding author.

"The amazing thing about PP1 is that no one has wanted to touch it for the most part as a drug target because PP1 is involved in nearly every biological process," Page said. "It's not like you could just target the PP1 active site for, let's say, diabetes because then you are going to affect drug addiction, Alzheimer's disease and all these other diseases at the same time."

In other words, make a medicine to block PP1 in one bodily context and you'd ruin it in all other contexts. Structural biologists such as Page and Brown co-author Wolfgang Peti have therefore been eager to learn what makes PP1 behave in specific ways in specific situations.

The key is the way PP1 binds with more than 200 different regulatory proteins. Scientists know of these proteins and know the sequences of amino acids that compose them, but they don't know their structure or how they actually guide PP1.

"The ability to predict how these PP1 interacting proteins bind PP1 from sequence alone is still missing," Page and her colleagues wrote in PNAS.

Now, through experiments in which her team including lead author Meng Choy combined NMR spectroscopy, X-ray crystallography and techniques in biochemistry, she has learned how PP1 b
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Contact: David Orenstein
david_orenstein@brown.edu
401-863-1862
Brown University
Source:Eurekalert  

Page: 1 2

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