Navigation Links
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 binds to a targeting protein called PNUTS, forming "binding motifs." That knowledge, combined with what she learned in earlier studies about two other targeting proteins NIPP1 and spinophilin has allowed her team to predict how PP1 binds with 43 of the 200 regulatory proteins that give it specific behavior.

"What this work in conjunction with two of our previous structures allowed us to do was to define two entirely new motifs," she said. "From that, comparing the sequences with the known proteins that interact with PP1 whose structures we don't have, we were able to predict that 20 percent of them likely interact in a way that is similar to these three proteins."

So by resolving the structure of just three proteins with PP1, Page now has the means to understand the binding of many proteins without having to resolve their structure. Instead she need only know the few motifs and the proteins' sequences.

As for PP1's interactions with the other 80 percent or so of regulatory proteins, those remain a mystery. But Page said the success her team has had in the lab working with PP1 and resolving key motifs makes her optimistic that those interactions can be solved, too.


'/>"/>
Contact: David Orenstein
david_orenstein@brown.edu
401-863-1862
Brown University
Source:Eurekalert  

Related biology news :

1. Markets Poised for Healthy 2014 as Biometrics Makes Strides in Technology Sector - Company Strengthens Board with Industrys Top Leaders
2. Duke engineers make strides toward artificial cartilage
3. Germ-fighting vaccine system makes great strides in delivery
4. CNIO participates in the ENCODE project: A stride forward in biomedical research
5. Research of zebrafish neurons may lead to understanding of birth defects like spina bifida
6. Finding common ground fosters understanding of climate change
7. Cell division finding could boost understanding of cancer
8. IMPRESSIONS: Advancing understanding of the consequences of high-end climate change
9. Understanding secondary light emission by plasmonic nanostructures may improve medical imaging
10. New DRI project aimed at understanding Mercury dynamics in the Arctic tundra
11. Reinterpreting origins, examining skeletal preservation, and understanding volcanics
Post Your Comments:
*Name:
*Comment:
*Email:
Related Image:
Big stride in understanding PP1, the ubiquitous enzyme
(Date:6/21/2016)... 21, 2016 NuData Security announced today that ... of principal product architect and that Jon ... customer development. Both will report directly to ... moves reflect NuData,s strategic growth in its product ... customer demand and customer focus values. ...
(Date:6/9/2016)... 2016 Paris Police Prefecture ... security solution to ensure the safety of people and operations ... the major tournament Teleste, an international technology group ... announced today that its video security solution will be utilised ... up public safety across the country. The system roll-out is ...
(Date:6/2/2016)... Perimeter Surveillance & Detection Systems, ... Infrastructure, Support & Other Service  The latest ... comprehensive analysis of the global Border Security market ... of $17.98 billion in 2016. Now: In ... in software and hardware technologies for advanced video surveillance. ...
Breaking Biology News(10 mins):
(Date:6/23/2016)... 2016 Houston Methodist Willowbrook Hospital has ... Association to serve as their official health care ... Willowbrook will provide sponsorship support, athletic training services, ... coaches, volunteers, athletes and families. "We ... Association and to bring Houston Methodist quality services ...
(Date:6/23/2016)... June, 23, 2016  The Biodesign Challenge (BDC), a ... ways to harness living systems and biotechnology, announced its ... in New York City . ... students, showcased projects at MoMA,s Celeste Bartos Theater during ... , MoMA,s senior curator of architecture and design, and ...
(Date:6/23/2016)... ... 2016 , ... STACS DNA Inc., the sample tracking software company, today announced ... has joined STACS DNA as a Field Application Specialist. , “I am thrilled ... COO of STACS DNA. “In further expanding our capacity as a scientific integrator, Hays ...
(Date:6/23/2016)... NEWPORT BEACH, Calif. , June 23, 2016 /PRNewswire/ ... offering new biological discoveries to the medical community, has ... and co-founder Matthew Nunez . "We ... provide us with the capital we need to meet ... funding will essentially provide us the runway to complete ...
Breaking Biology Technology: