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UCSD study reveals the regulatory mechanism of key enzyme
Date:9/20/2007

Research conducted at the University of California, San Diego (UCSD) School of Medicine has shed new light on the structure and function of one of the key proteins in all mammalian cells, protein kinase A (PKA), an enzyme which plays an essential role in memory formation, communication between nerve cells, and cardiac function.

Utilizing a process called x-ray crystallography, the scientists solved the structure of the large PKA complex, revealing a totally new structure that shows PKAs amazing ability to function as a scaffold, that supports and controls the release of chemicals involved in transmitting signals. The structure is shown in the September 21 issue of the journal Cell, featuring the study that describes the dynamic regulatory subunit of PKA.

PKA belongs to a large superfamily of proteins whose activity is regulated by an important small molecule, cyclic AMP (cAMP), in the cell. Protein kinases transmit chemical signals within the cell to regulate a host of functions, such as cell growth or metabolism. Certain protein kinases have been implicated in the uncontrolled growth of cells; for example, when PKA somehow stays on, its prolonged activation can lead to cardiac disease and breast cancer.

By revealing its highly accurate three-dimensional structure, the UCSD scientists have shown how PKA is inhibited and activated by cAMP. PKA contains two components, the regulatory and catalytic subunits. When the subunits are together in the absence of cAMP, the signaling is turned off; when the two parts break apart after being activated by cAMP, PKA is turned on.

We knew how the two subunits, the catalytic and regulatory subunits, looked as separate entities. But we didnt understand how they actually fit together and are activated by cAMP until we saw this structure, said Susan Taylor, Ph.D., Howard Hughes Medical Institute Investor and professor of pharmacology at UCSD School of Medicine, who headed the study.
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Contact: Debra Kain
ddkain@ucsd.edu
619-543-6163
University of California - San Diego
Source:Eurekalert

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