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Secrets of a precision protein machine
Date:4/15/2011

nt 100 degrees. The helicity of the double strand positions the 5' flap, threading it through the arch. The helicity of the double strand, plus the binding of the 3' overhang, also prompts the disordered parts of FEN1 to close up. Finally two paired bases on the 5' flap are pulled apart over the metal ions, triggering incision at the scissile phosphate."

She adds, "Many biologists still have the model of FEN1 sliding down the 5' flap in their heads, so our model with no sliding, but rather pushing the 5' flap through the narrow arch is 'Copernican.' It requires a whole new way of looking at this pivotal protein activity."

Says Tainer, "Knowing how the parts move, we know how we can interfere with them. FEN1 plays a dual role in cancer it is essential to health, but it's also overproduced in many cancers and associated with aggressive tumors. By designing drugs that induce changes in specific structures rather than active sites which may be nonspecific we have hope for more effective, more targeted, and less damaging treatment."


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Contact: Paul Preuss
paul_preuss@lbl.gov
510-486-6249
DOE/Lawrence Berkeley National Laboratory
Source:Eurekalert  

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