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Scientists prove X-ray laser can solve protein structures from scratch
Date:11/24/2013

don't form crystals that can be deciphered with existing techniques.

This work is the latest in a rapid progression of important advances at LCLS, which began operations for users in 2010. For example, last year researchers used LCLS to determine the structure of an enzyme that can hold African sleeping sickness in check, which makes it a promising drug target. However, those previous studies relied on data from similar, known structures to fill in common data gaps.

For this study the researchers chose lysozyme, whose structure has been known for decades, because it offered a good test of whether their method produced accurate results. They soaked lysozyme crystals in a solution containing gadolinium, a metal that bonded with the lysozyme to produce a strong signal when subjected to the intense X-ray light. It was this signal from the gadolinium atoms that enabled exact reconstruction of the lysozyme molecule.

The team hopes to adapt and refine the technique to explore more complex proteins such as membrane proteins, which serve a range of important cellular functions and are the target of more than half of all new drugs in development. Only a small fraction of the thousands of membrane proteins have been completely mapped.

"This study is an important milestone on which the field will build further," said John R. Helliwell, emeritus professor of chemistry at the University of Manchester and formerly a director of the Synchrotron Radiation Source at Daresbury Laboratory in England. "The X-ray laser is bringing new opportunities and new ideas for 3-D structure determination of ever-smaller samples. The use of computers to automate this process is a triumph."

Barends said the latest results are a remarkable achievement, given that it took just a few years for LCLS to reach this milestone. "Further improvements in X-ray detectors, software and crystal formation and delivery techniques should enable more discoveries in the comi
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Contact: Andy Freeberg
afreeberg@slac.stanford.edu
650-926-4359
DOE/SLAC National Accelerator Laboratory
Source:Eurekalert  

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