Heavy metal research is music to biologists' ears

Crab and lobster are more than perennial summer favorites--they are also a good dietary source of copper. Yes, the stuff of pennies is crucial for life--the metal copper is an important helper to many cellular enzymes, including superoxide dismutase (SOD), which sops up dangerous "free radicals" that accumulate inside cells. Defects in SOD have been linked to some inherited forms of amyotrophic lateral sclerosis, also known as Lou Gehrig's disease.

In an important advance in understanding the molecular underpinnings of this disease, scientists supported by the National Institute of General Medical Sciences (NIGMS) have deciphered the three-dimensional structure of a yeast copper "chaperone" protein, a molecule that transports copper to the SOD enzyme. Although copper is necessary for life, it is a potentially toxic "heavy metal" that--in the wrong cellular locale--can damage other molecules, and in some cases can even cause disease. As the name suggests, the copper chaperone protein protects copper from unwanted cellular interactions and safely delivers it to its destination.

The work also identifies a potential target for developing drugs to treat Lou Gehrig's disease, a uniformly fatal condition.

The research report appears in the August 1999 issue of the journal Nature Structural Biology.

A little over six years ago, scientists first linked Lou Gehrig's disease to SOD by showing that some people with the disease had "misspellings" in the gene that encodes SOD. The finding prompted a series of studies aimed at determining how copper gets inserted into this prevalent cellular enzyme. In 1997, Dr. Valeria Culotta of The Johns Hopkins University, collaborating with Dr. Thomas O'Halloran of Northwestern University, first discovered a protein that ferries copper molecules throughout a yeast cell; they coined it a copper chaperone. (Further research has shown that the yeast chaperone is very similar to its counterpart in humans.) Around the s

Contact: Alison Davis
NIH/National Institute of General Medical Sciences

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