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Scientists characterize protein essential to survival of malaria parasite
Date:1/6/2012

nematode, or microscopic roundworm, but many nematodes are parasitic and cause disease in plants, livestock and people.

During this project, Lavanya Palavalli, a summer intern working with Jez, crystallized the C. elegans version of the enzyme. The job of the enzyme, phosphoethanolamine methyltransferase, thankfully abbreviated to PMT, is to add methyl groups to a starting molecule, phosophoethanolamine.

"When Soon Goo Lee later took up the project," says Jez, "the plan was to try to grow better crystals of the C. elegans protein, ones good enough to get readable X-ray diffraction patterns.

Two years later, the crystals were looking better but still not good enough.

So Jez suggested that Lee go after homologous (look-alike) proteins in other organisms. "Even though the proteins are homologous, each has a different amino acid sequence and so will behave differently in the crystallizations," Jez says. "Lee went from working with two C. elegans proteins to three plant proteins, two other nematode proteins and then the Plasmodium protein," Jez says.

"He took all six of those PMT versions into the crystallization trials to maximize his odds," Jez says.

"To crystallize a protein," Jez says, "we put a solution of a salt or something else that might work as a desiccant in the bottom of a small well. And then we put a drop of our liquid protein on a microscope cover slip and flip it over the top of the well, so the drop of protein is hanging upside down in the well."

"What we're trying to do is to slowly withdraw water from the protein. It's exactly like making rock candy, only in that case, the string hanging into the jar of sugar solution helps to withdraw water," he says.

The difference is that sugar wants to form crystals and proteins are reluctant to do so.

"There are 24 wells to a tray, and we usually screen 500 wells per protein at first," Jez says. "Lee ha
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Contact: Diana Lutz
dlutz@wustl.edu
314-935-5272
Washington University in St. Louis
Source:Eurekalert  

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