Navigation Links
Key enzyme discovered to be master regulator in protein-protein reactions
Date:3/24/2010

PROVIDENCE, R.I. [Brown University] Protein phosphorylation is a process by which proteins are flipped from one activation state to another. It is a crucial function for most living beings, since phosphorylation controls nearly every cellular process, including metabolism, gene transcription, cell-cycle progression, cytoskeletal rearrangement and cell movement.

Due to its importance in biology, scientists have wanted to learn more about protein phosphorylation and how proteins know when and how to become phosphorylated or dephosphorylated. Think of it like choosing the right dance partner who knows your moves so intimately that the choreography is seamless. Biologists have learned that interactions by kinases (enzymes that add a phosphate to a protein) are highly regulated. Each of the 428 human serine/threonine kinases interact only with certain substrate proteins, and they pick their "partners" unfailingly. But for the reverse reaction, called dephosphorylation (removing a phosphate from a protein), only about 40 phosphatases are available to interact with all substrate proteins. In fact, just one of them, protein phosphatase 1 (PP1), is believed to be responsible for up to 65 percent of dephosphorylation reactions.

The question then is how PP1, a generalist, knows which substrate proteins to interact with. New research by Wolfgang Peti, the Manning Assistant Professor of Medical Science and assistant professor of chemistry, reported in a paper published online in Nature Structural & Molecular Biology, helps to answer that question. Peti and colleagues at Brown and Yale University have discovered that PP1 "chooses" proteins in dephosphorylation reactions based on which of its binding sites is available for the interaction to occur. The finding is important, because erroneous PP1 regulation can cause numerous diseases, including cancer (chromatin remodeling), diabetes (glycogen) and Parkinson's (LTP).

"There are thousands of (peer-reviewed) papers out there, but nobody understood how PP1 is regulated," said Peti. "It is in fact a master regulator. We have identified now how it works."

To obtain their results, the team showed for the first time how PP1 is bound to a regulator protein, spinophilin. Using nuclear magnetic resonance spectroscopy and X-ray crystallography, the researchers examined the spinophilin-PP1 complex's structure. The scientists saw that spinophilin had attached itself to one of three substrate binding sites on PP1, called the C-terminal substrate binding groove. Examined at the atomic scale, it appears as if spinophilin is a many-tentacled beast that has woven itself into the C-terminal substrate binding groove, effectively blocking any substrate requiring this groove from interacting with PP1.

That leaves only two other binding sites, the acidic and hydrophobic substrate binding grooves. "Any substrate that needs the C-terminal is out of the game," Peti said.

By narrowing the binding sites from three to two, PP1 is in effect becoming more selective, Peti noted. "What that means is PP1 is equally tightly controlled as kinases are," he said.

"Now we know how PP1 is regulated," Peti added. "What simply happens is we don't create more enzymes. We create more protein complexes (holoenzymes) that increase the specificity of PP1."


'/>"/>

Contact: Richard Lewis
Richard_Lewis@brown.edu
401-863-3766
Brown University
Source:Eurekalert  

Related biology news :

1. MSU scientists unlock key enzyme using newly created cool method
2. Enzyme deficiency protects hepatitis C patients from treatment-related anemia
3. Scientists identify critical enzyme in healthy heart function
4. Enzyme necessary for development of healthy immune system
5. Newly identified enzymes help plants sense elevated CO2 and could lead to water-wise crops
6. Tiny particles can deliver antioxidant enzyme to injured heart cells
7. Genencor Wins The American Institute of Chemical Engineers (AIChE) Sustainable Energy Award For Accellerase(R) Cellulosic Ethanol Enzymes
8. UCLA researchers reconstitute enzyme that synthesizes cholesterol drug lovastatin
9. Scientists are first to observe the global motions of an enzyme copying DNA
10. New artificial enzyme safer for nature
11. Developing enzymes to clean up pollution by explosives
Post Your Comments:
*Name:
*Comment:
*Email:
Related Image:
Key enzyme discovered to be master regulator in protein-protein reactions
(Date:3/24/2017)... Research and Markets has announced the addition of the "Global ... to 2025" report to their offering. ... The Global Biometric Vehicle Access System Market ... the next decade to reach approximately $1,580 million by 2025. ... for all the given segments on global as well as regional ...
(Date:3/23/2017)... 2017 Research and Markets has announced the ... Trends - Industry Forecast to 2025" report to their offering. ... The Global ... of around 8.8% over the next decade to reach approximately $14.21 ... market estimates and forecasts for all the given segments on global ...
(Date:3/22/2017)... , March 21, 2017 ... Cloud used by retailers such as 1-800-Flowers and ... platform — Product Recommendations and Replenishment. Using Optimove,s machine ... more personalized product and replenishment recommendations to their ... also on predictions of customer intent drawn from ...
Breaking Biology News(10 mins):
(Date:6/19/2017)... NJ (PRWEB) , ... June 19, 2017 , ... ... innovative solutions for clinical development reported today that it is launching two new ... The company will be demonstrating new capabilities at the DIA 2017 Annual Meeting ...
(Date:6/19/2017)... ... June 19, 2017 , ... A colony of healthy honey ... and tissues by delivering pollen and nectar containing nutrients necessary for growth and survival. ... healthy. , Many recent indicators point to a decline in honey bee health. Sick ...
(Date:6/16/2017)... ... June 16, 2017 , ... Cambridge Semantics ... that its Anzo Smart Data Lake® (Anzo SDL) solution was named a ... 2017 Software & Information Industry Association (SIIA) CODiE Awards. , Finalists represent ...
(Date:6/15/2017)... (PRWEB) , ... June 15, 2017 , ... ... synthetic auxin herbicides give farmers new options for managing Palmer amaranth and other ... America (WSSA) say special precautions are necessary. Auxin herbicides are known to drift ...
Breaking Biology Technology: