Two recent developments allowed them to overcome this problem: a new way to grow crystals of the enzyme for analysis and the ability to analyze those tiny crystals with the LCLS X-ray laser, whose pulses are so intense and fast that they capture structural information before a sample is damaged.
The researchers grew the crystals inside live insect cells, freezing the enzyme in its natural inhibited state. Then they streamed the crystals into the laser's path, producing patterns in a detector that were used to reconstruct the enzyme and its inhibitor in 3-D and at nearly atomic scale.
"In my opinion, we provided the most complete blueprint available so far for the development of a synthetic inhibitor to block this enzyme," Redecke said. "Whether it will be successful is hard to say, but the odds are significantly increased by this structural data."
Redecke said his research team is working to crystallize proteins relevant to other parasites and viruses, including strains of hepatitis and flu, that could also be studied at LCLS, and he expects this field of research to grow.
"Our study will encourage others to use free-electron lasers to obtain new structural information of biologically relevant molecules," Redecke said.
|Contact: Andy Freeberg|
DOE/SLAC National Accelerator Laboratory