CHAPEL HILL -- Without help from a key enzyme called OMP decarboxylase, 78 million years would be needed at room temperature for a molecule central to all living things to shed half the carbon dioxide attached to it.

When this chemical supercharger does its job, however, the process can occur some 30 times in a single second, University of North Carolina at Chapel Hill biochemists Anna Radzicka and Richard V. Wolfenden reported in 1995. That's the greatest acceleration ever found for a reaction jump-started by an enzyme.

Now, the three-dimensional structure of the enzyme has been determined through a collaboration between Glaxo Wellcome Inc. scientists and UNC-CH researchers. The reaction that the enzyme works on is the last intermediate step in synthesizing UMP -- one of the four letters of the genetic code and is therefore needed by all organisms for growth.

A report on the research appears in Tuesday's (Feb. 29) issue of the Proceedings of the National Academy of Sciences. UNC-CH School of Medicine authors are biochemistry graduate student Brian Miller and Wolfenden, Alumni Distinguished professor of biochemistry and biophysics. Glaxo Wellcome authors are Drs. Steven A. Short, Anne M. Hassell and Michael V. Milburn.

"The molecule's crystal structure, combined with other information, reveals that the enzyme OMP decarboxylase operates by a disarmingly simple and unprecedented mechanism," Wolfenden said. "We were imagining something more elaborate, but what we found was elegant simplicity."

All enzymes work in the body at similar rates and must act pretty much in unison for organisms to survive, he said. What differs from one enzyme to another is that some have much harder jobs than others.

"This one has the hardest job we know about -- changing a reaction that takes a good fraction of the lifetime of the Earth to one that occurs as fast as the shutter release in a single-lens reflex camera," Wolfenden said.

Miller, who is earning
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Contact: David Williamson
David_Williamson@unc.edu
919-962-8596
University of North Carolina at Chapel Hill
27-Feb-2000