In a search for skin cancer treatments, chemists at the University of Notre Dame have constructed a computer model of the chemical structure of an enzyme that many organisms use to repair DNA damaged by ultraviolet light. Their findings are reported in the June 9 issue of the Journal of the American Chemical Society and are now on the journal's website at http://pubs.acs.org/journals/jacsat/index.html.
According to Olaf Wiest, assistant professor of chemistry and biochemistry and principal investigator, the ultimate goal of the research is to produce an artificial enzyme for human use that could repair DNA damaged by ultraviolet light in humans. Such damage leads to certain types of skin cancer, which have reached almost endemic proportions. Skin cancer is now the most common form of cancer in the United States, with an estimated 1.4 million cases diagnosed annually. According to Wiest, the number of skin cancer patients has risen steadily over the past 20 years.
The computer model provides atomic details of the binding interactions of damaged DNA and DNA photolyase, the repair enzyme of the bacterium Escherichia coli. According to Wiest, the model provides new insights into which parts of the enzyme are important for electron transfer that repairs the damage.
DNA photolyase and other mechanisms are used by many organisms, suc h as yeast and algae -- but not humans -- to protect against damage by ultraviolet light. By understanding how the protection mechanisms in these organisms work, scientists may be able to develop ways to protect humans from these types of skin cancer, Wiest says.
"To the best of our knowledge, our model is the first to explain all the pertinent experimental data -- binding and alkylation studies, spectroscopic data, rate constants and mutagenesis results -- in a consistent fashion," Wiest says. "It is of course still a model, but in the absence of an x-ray structure of the enzyme-substrate complex, it provides the framework to think about the mode of action of the enzyme, make predictions, and develop experiments to test these predictions. Such a framework was not previously available."
This research is funded by the National Institutes of Health.
Computer simulated pictures (not under by JACS copyright) are available at http://www.nd.edu/~owiest/photolyase/pics.html.
Materials provided by University Of Notre Dame. Note: Content may be edited for style and length.
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