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December 3, 2012
Stanford's Free Electron Laser Blasts Away
Here's another next-generation X-ray crystal paper, this time using a free electron laser X-ray source. That's powerful enough to cause very fast and significant radiation damage to any crystals you put in its way, so the team used a flow system, with a stream of small crystals of T. brucei cathepsin B enzyme being exposed in random orientations to very short pulses of extremely intense X-rays. (Here's an earlier paper where the same team used this technique to obtain a structure of the Photosystem I complex). Note that this was done at room temperature, instead of cryogenically. The other key feature is that the crystals were actually those formed inside Sf9 insect cells via baculovirus overexpression, not purified protein that was then crystallized in vitro.
Nearly 4 million of these snapshots were obtained, with almost 300,000 of them showing diffraction. 60% of these were used to refine the structure, which out at 2.1 Angstroms, and clearly showed many useful features of the enzyme. (Like others in its class, it starts out inhibited by a propeptide, which is later cleaved - that's one of the things that makes it a challenge to get an X-ray structure by traditional means).
I'm always happy to see bizarre new techniques used to generate X-ray structures. Although I'm well aware of their limitations, such structures are still tremendous opportunities to learn about protein functions and how our small molecules interact with them. I wrote about the instrument used in these papers here, before it came on line, and it's good to see data coming out of it.
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