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Fighting sleeping sickness with X-ray lasers
Date:12/21/2012

This press release is available in German.

Using the world's most powerful X-ray free-electron laser, an international team of researchers, including scientists of the Max Planck Institute for Medical Research in Heidelberg, has obtained new insight into the structure of a medicinally important protein that may serve as a blueprint for the development of drugs to fight sleeping sickness. Science magazine have chosen the experimental study as one of the top ten scientific breakthroughs of the year.

Sleeping sickness is caused by the unicellular organism Trypanosoma brucei that is transmitted by tsetse flies. The disease kills about 30,000 people word-wide each year. The currently available drugs against the disease are of limited efficacy and can have severe side effects. Moreover, resistance against them is increasing. A promising drug target is the protein Cathepsin B whose enzymatic activity is vital for the parasite's survival. Inhibitors of Cathepsin B need to be highly specific against the trypanosomal variant because it resembles the human form. The featured work provides detailed insight into the structure of trypanosomal Cathepsin B in a natively inhibited form that might serve as a blueprint for the rational design of drugs. The biologically important form of the protein was obtained by a trick: instead of crystallizing the protein in plastic trays in the lab, it was crystallized in vivo in the cells that produced the protein. This approach provides natively modified proteins, but the crystals obtained are tiny.

The use of the X-ray free-electron laser (FEL) at Stanford was essential for the work. Protein structures are typically determined by exposing crystals of the protein to X-rays. Unfortunately, many of the most interesting proteins, such a membrane proteins, do not form crystals of sufficient size for analysis
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Contact: Dr. Ilme Schlichting
ilme.schlichting@mpimf-heidelberg.mpg.de
49-622-148-6500
Max-Planck-Gesellschaft
Source:Eurekalert  

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Fighting sleeping sickness with X-ray lasers
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