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First glimpse of DNA binding to viral enzyme

UPTON, NY -- Scientists at the U.S. Department of Energy's Brookhaven National Laboratory and the Albert Einstein College of Medicine have produced the first molecular-scale images of DNA binding to an adenovirus enzyme -- a step they believe is essential for the virus to cause infection. The images, which appear on the cover of the October 2004 issue of Molecular and Cellular Proteomics, show how binding to DNA may stimulate the enzyme and are already being used to design new antiviral drugs to block this interaction.

"We were quite surprised to see that DNA actually stimulated the activity of the enzyme," said Brookhaven biologist Walter Mangel, a co-author on the paper. "If we can block this interaction, we should be able to prevent the virus from replicating, and thereby thwart infection."

Adenoviruses cause respiratory, gastrointestinal, and eye infections, including highly contagious viral pink eye. Some adenovirus eye infections lead to blindness. Respiratory epidemics of adenovirus are often prevalent on army bases. And in patients with compromised immune systems, such as those infected with human immunodeficiency virus (HIV), an opportunistic adenovirus infection can be deadly.

During infection, adenovirus makes an enzyme called a protease, which cleaves or degrades viral "scaffolding" proteins to complete the maturation of newly synthesized virus particles. Mangel and others have been working to understand all the steps necessary for this enzyme's function, looking for new ways to stop its action and, therefore, block an adenovirus infection (see: http://www.bnl.gov/discover/Spring_04/anti_viral_1.asp).

The scientists didn't expect the viral DNA to bind to the protease, but they figured they should look just to rule out such an interaction. "It was something we had to do, to make sure they did not interact," Mangel said. The discovery that the v
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Contact: Karen McNulty Walsh
kmcnulty@bnl.gov
631-344-8350
DOE/Brookhaven National Laboratory
13-Sep-2004


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