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Scripps research scientists model 3D structures of proteins that control human clock
Date:4/10/2009

In an Early Edition issue of The Proceedings of the National Academy of Sciences (PNAS) on April 9, 2009, the researchers report that they have been able to determine the molecular structure of a plant photolyase protein that is surprisingly similar to two cryptochrome proteins that control the "master clock" in humans and other mammals. They have also been able to test how structural changes affect the function of these proteins.

"The plant photolyase structure provides a much better model to use to study how the cryptochrome proteins in the human clock function than we have ever had before," says the study's lead investigator, Kenichi Hitomi, Ph.D., a postdoctoral research fellow at Scripps Research. "It's like knowing for the first time where the engine is in a car. When you know what the most important parts of the protein are, then you can begin to figure out how it functions."

And when scientists understand that, they can begin to fix the clock when needed, adds senior author Elizabeth Getzoff, Ph.D., professor in the Department of Molecular Biology and member of The Skaggs Institute for Chemical Biology at Scripps Research.

"In addition to decoding how the clock works, a long-term goal is to develop a drug to help people who can't reset their clock when they need to, like people who work night shifts or travel long distances," she says. "Having the three-dimensional protein is a great step forward in both of those pursuits."

To date, it has been impossible to capture a crystal structure of the cryptochrome proteins that control the mammalian circadian clock because they aren't in a sufficiently stable state, Hitomi says. So, working with a team of investigators from both Scripps Research and from other institutions, including two universities in Japan, Hitomi turned to Arabidopsis thaliana, a plant native to Europe and Asia that has one of the smallest genomes of all plants, and so is often used as a
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Contact: Keith McKeown
kmckeown@scripps.edu
858-784-8134
Scripps Research Institute
Source:Eurekalert

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