{ Theoretical chemists at Rutgers University use Alliance resources to search for the elusive mechanism of one of the world's most proficient enzymes.

How do they do it? It's a question we ask about all our champions—whether it's Ali dancing about the ring or Jones blazing her way through the 100-meter dash. Unlike the typical sports fan, however, researchers watching one of the world's most proficient enzymes in action aren't content to sit awestruck on the sidelines. Instead, they're in the lab and using Alliance supercomputers to figure out not only that enzyme's mechanism, or the way it accelerates a chemical reaction, but also the nature of the uncatalyzed chemical reaction that the enzyme alters.

The champion enzyme is orotidine 5'-monophosphate decarboxylase. Thankfully it's also known as ODCase. ODCase catalyzes orotic acid's decay into uracil, a notoriously slow process.

"The half life of the reaction is about 78 million years," says Jeehiun Lee, an assistant professor of chemistry at Rutgers University. "We're talking about a geological timescale here. To even get that figure, Richard Wolfenden [a biochemistry professor at the University of North Carolina] had to heat the heck out of it [to increase the reaction rate without resorting to a catalyst] and then extrapolate to room temperature."

 

ODCase speeds the transformation by a factor of 1017. This rate change is extreme, to be sure, but that's not the only reason researchers are interested in ODCase and the orotic-acid-to-uracil reaction. Uracil is one of RNA's four bases, making it an essential piece of any living thing.

For Lee and others in the pure research game, a fundamental understanding of the genesis of such a seminal biological species would be enough. But a clear picture of the process would be a boon for more application-oriented researchers, too. If Lee's team and their kindred can figure out the mechanism by which ODCase works, application scientists can step in. They might build, or at least begin to devise, inhibitors that block the formation of uracil when DNA synthesis goes awry. Block the biosynthetic process in such a case, and you're on your way to blocking tumor growth. >>



Access Online | Posted 10-8-2002