New insight into the controls on a go...( Scientists at St. Jude Children's Re...)

Scientists at St. Jude Children's Research Hospital have gained new insights into regulation of one of the body's enzyme workhorses called calpains.

As the cell's molecular overachievers, calpains function in many cellular processes, including the movement of cells in tissues, the death of damaged cells, insulin secretion, and brain cell and muscle function. The downside of this broad set of responsibilities is that defective or overactive calpains have been linked to an array of disorders, including a form of muscular dystrophy, Type 2 diabetes, gastric cancers, Alzheimer's and Parkinson's diseases, cataracts, and the death of both heart muscle in heart attacks and of brain tissue in stroke and traumatic brain injury.

"Our basic findings on calpain regulation could add useful pieces to the puzzles of these disorders and perhaps reveal targets for drugs to treat them," said Douglas Green, Ph.D., chair of the St. Jude Department of Immunology.

Calpains are triggered by calcium flowing into the cell. This process induces the enzyme to snip apart many target proteins, as part of the cell's regulatory machinery. However, such a critical enzyme needs ultra-precise control, which is the job of another protein called calpastatin. A central question has been how calpastatin is so exquisitely specific in attaching to calpain and inhibiting itessentially ignoring other highly similar enzymes in the cell.

In an article published in the November 20, 2008, issue of the journal Nature, Green and his colleagues report new information on the specificity of calpastatin.

"Previous studies on calpastatin had revealed how a few of the parts of the calpastatin molecule attach to calpain in the inhibition process," said Green, the report's senior author. "However, there was no overall picture of calpastatin that revealed how it was so precise in its attachment and potent in its function."

To obtain that overall picture,
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