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

model organism to study genes.

Like all plants, this plant contains proteins known as photolyases, which use blue light to repair DNA damage induced by ultraviolet light. Photolyases have also been found in bacteria and in some animals, but not in human cells. Humans and mammals, on the other hand, possess a homologous protein known as cryptochrome that modulates the circadian clock.

"This is an amazing, and very puzzling, family of proteins, because they do one thing in plants and quite a different thing in mammals, yet these cousins all have the same structure and need the same cofactor, or chemical compound, to become activated," Getzoff says.

"All of these proteins were probably originally responses to sunlight," Hitomi adds. "Sunlight causes DNA damage, so plants need to repair this damage, and they also need to respond to sunlight and seasons for growth and flowering. The human clock is set by exposure to sunlight, but also by when we eat, sleep, and exercise."

In this study, Hitomi set about producing proteins from the Arabidopsis thaliana genes that produce two related photolyase enzymes. These genes had been cloned earlier in the laboratory of co-author Takeshi Todo, Ph.D., of Kyoto University, with whom Hitomi previously studied.

He moved the gene from the plant into E. coli bacteria to produce a lot of the protein, which he then crystallized to determine the atomic structure by using X-ray diffraction. The researchers then produced a variety of mutant proteins in order to test the functional structure of the enzymes.

"We can now look at things that are the same and different between human and mouse cryptochromes and plant photolyases," says Hitomi. "Our results provide a detailed, comparative framework for biological investigations of both of these proteins and their functions."

Not only do the findings have the potential to form the basis of drugs that can ease jet lag and regulate drug metabol
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Contact: Keith McKeown
kmckeown@scripps.edu
858-784-8134
Scripps Research Institute
Source:Eurekalert

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