Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Understanding PP1, the ubiquitous enzyme

04.03.2014

The enzyme PP1 has a key role in many of the body’s healthy functions and diseases. It’s so generally important that drug developers dare not target it. In a new study in the Proceedings of the National Academy of Sciences, Brown University scientists report a big leap in understanding how PP1 interacts with other proteins to behave specifically in distinct situations. That could lead to medicines that target it for precise benefits.

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.


The Enzyme PP1, the tan mass above, is everywhere in the body and has a role in nearly every biological process. That role is shaped more than 200 regulatory Proteins that bind to PP1, including one called PNUTS. blue and pink above. Credit: Page lab/Brown University

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.

In addition to Page, Choy, and Peti, the paper’s other authors are Martina Hieke, Ganesan Senthil Kumar, Greyson Lewis, Kristofer Gonzalez-DeWhitt, Rene Kessler, Benjamin Stein, and Manuel Hessenberger of Brown and Angus Nairn of Yale.

The National Institute of General Medical Sciences (grant R01GM098482) supported the research.

Editors: Brown University has a fiber link television studio available for domestic and international live and taped interviews, and maintains an ISDN line for radio interviews. For more information, call (401) 863-2476.

David Orenstein | EurekAlert!
Further information:
http://news.brown.edu/pressreleases/2014/03/pp1

Further reports about: PP1 diseases enzyme motifs proteins regulatory sequences structure

More articles from Life Sciences:

nachricht MicroRNA helps cancer evade immune system
19.09.2017 | Salk Institute

nachricht Ruby: Jacobs University scientists are collaborating in the development of a new type of chocolate
18.09.2017 | Jacobs University Bremen gGmbH

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

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...

Im Focus: Quantum Sensors Decipher Magnetic Ordering in a New Semiconducting Material

For the first time, physicists have successfully imaged spiral magnetic ordering in a multiferroic material. These materials are considered highly promising candidates for future data storage media. The researchers were able to prove their findings using unique quantum sensors that were developed at Basel University and that can analyze electromagnetic fields on the nanometer scale. The results – obtained by scientists from the University of Basel’s Department of Physics, the Swiss Nanoscience Institute, the University of Montpellier and several laboratories from University Paris-Saclay – were recently published in the journal Nature.

Multiferroics are materials that simultaneously react to electric and magnetic fields. These two properties are rarely found together, and their combined...

Im Focus: Fast, convenient & standardized: New lab innovation for automated tissue engineering & drug

MBM ScienceBridge GmbH successfully negotiated a license agreement between University Medical Center Göttingen (UMG) and the biotech company Tissue Systems Holding GmbH about commercial use of a multi-well tissue plate for automated and reliable tissue engineering & drug testing.

MBM ScienceBridge GmbH successfully negotiated a license agreement between University Medical Center Göttingen (UMG) and the biotech company Tissue Systems...

Im Focus: Silencing bacteria

HZI researchers pave the way for new agents that render hospital pathogens mute

Pathogenic bacteria are becoming resistant to common antibiotics to an ever increasing degree. One of the most difficult germs is Pseudomonas aeruginosa, a...

Im Focus: Artificial Enzymes for Hydrogen Conversion

Scientists from the MPI for Chemical Energy Conversion report in the first issue of the new journal JOULE.

Cell Press has just released the first issue of Joule, a new journal dedicated to sustainable energy research. In this issue James Birrell, Olaf Rüdiger,...

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

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

19.09.2017 | Event News

New quantum phenomena in graphene superlattices

19.09.2017 | Physics and Astronomy

A simple additive to improve film quality

19.09.2017 | Power and Electrical Engineering

VideoLinks
B2B-VideoLinks
More VideoLinks >>>