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Complex Movements of Enzymes Targeted for Anti-obesity, Anti-cancer Drugs
These enzymes are integrated into a single molecular complex known as fatty acid synthase, which is regarded as a potential target for developing new anti-obesity and anti-cancer drugs.
"Fatty Acid Synthase is a remarkably complex structure. It contains all of the components needed to convert carbohydrates into fat," said Dr. Stuart Smith, of Children's Hospital Oakland Research Institute.
"We have suspected for some time that the enzyme complex is extremely flexible, which makes it difficult to analyze using X-ray crystallography. Last year the X-ray structure of the complex was solved by a group in Switzerland, but this structure provided only a snapshot of the complex in one of its many poses. We were able to use state-of-the-art electron microscopy to obtain images of the complex in many of its different conformations and assemble these images into a movie that displays the full range of motion of the components of the complex," the researcher added.
Many drug makers are focusing on inhibitors of fatty acid synthase because they are known to block the conversion of carbohydrates into fat and suppress appetite as well as slow the growth of cancer cells.
The researchers are of the opinion that structural information garnered from X-ray and electron microscope images may aid in the design of more effective inhibitors that could be used therapeutically.
A research article on the study has been published in the journal Nature Structural and Molecular Biology.
Source-ANI
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