FOR IMMEDIATE RELEASE January 17, 1997
Contact:
Terence L. Day -- 509/335-2806 (Work)
[email protected] 509/334-1619 (Home)
Written by Mary Aegerter
NEW CLASS OF PROTEINS DISCOVERED AT WSU
This week's "Science" magazine features a major article
by Washington State University Professor of Biochemistry
Norman G. Lewis and co-workers on their discovery of the
first member of an apparent new class of proteins.
These proteins help explain how nature controls free-
radical chemistry, something scientists in laboratories have had
difficulty doing.
The findings have potentially broad applications, extending even
to human medicine.
Nature's control of free-radical chemistry is a mystery
because scientists have had enormous difficulty in controlling
these reactions.
"Always various mixtures have formed instead," says
WSU's Lewis. "Free-radical reactions are often blamed for the
onset of various medical disorders, such as cancers, as well as
for the unwanted degradation of synthetic materials.
"On the other hand, nature uses this bio-chemistry
extensively and exquisitely to link almost 40 percent of its
organic constituent in the biosphere," Lewis said.
The WSU group discovered a protein that they believe
helps guide free-radical coupling reactions to give only a
specific product, in their case pinoresinol.
Pinoresinol is a lignan that is an important precursor of
several cancer-preventing and cancer-treating lignans.
"The importance of this discovery goes far beyond
making this lignan," Lewis says. Many other substances in
nature are made by free-radical reactions. These include
wood, cork, the skin pigment melanin, the outer skeleton of
insects, and fungal fruiting bodies such as mushrooms.
Each of these substances may have its own guiding
protein to insure it is made in an orderly fashion.
"Our problem was knowing what to look for," says
Laurence Davin. Davin is program director for Lewis's lab and
co-author of the paper published in "Science". Co-workers
Huai-Bin Wang, Anastasia Crowell, Diana Bedgar, Diane Martin
and Simo Sarkanen also were co-authors on the article.
Now that the first protein has been found, the search for
others should be easier.
This class of proteins, which they term "dirigent proteins"
from the Latin "dirigere" (to align or guide), should prove
valuable in the laboratory.
"Until now, the kind of reaction we're looking at for
pinoresinol, getting a specific product rather than a mixture, is
something that the chemist hasn't been able to do in the lab,"
says Davin. It gives scientists a way to make lignans the same
way the plant does.
Davin helps coordinate the project that resulted in the
discovery of dirigent proteins, using forsythia to study how
plants make lignans. In plants, some lignans are part of a
plant's defenses against a variety of organisms. Other lignans
are used to fight cancers and viruses in humans, or to provide
protection against the onset of cancers and other diseases.
Pinoresinol is made in a three-step process. First two
molecules of an alcohol are modified by an enzyme, then they
are aligned by the dirigent protein and linked. Without the
dirigent protein, the product will at best be a combination of
pinoresinol, each a mirror image of the other and each
functionally distinct.
Forsythia makes only the one pinoresinol form it needs.
But laboratory test tube assemblies before the discovery of the
dirigent protein resulted in a mixture not only of the two forms
of pinoresinol, but also including three other mirror image pairs.
The desired pinoresinol was only one of the eight products in
the tube, and had to be separated and purified from the
mixture.
"We knew that the forsythia had something that no
laboratory had," says Davin. But even though they knew the
something was there, it proved difficult to find.
Now that they have identified the first dirigent protein,
Lewis and his colleagues are looking for others in plants. They
expect to find them in many different plant species, and they
expect to find different dirigents in any one species, such as
forsythia. That's because forsythia makes a variety of lignans
precisely, not just pinoresinol, and the protein that helps make
pinoresinol does not help make any other lignan they've yet
examined.
"Science" is the official publication of the American
Association for the Advancement of Science. The four-page
article reporting the lab's discovery is entitled "Stereoselective
Bimolecular Phenoxy Radicl Coupling by an Auxiliary (Dirigent)
Protein Without an Active Center."
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