The scientists have shown that the enzyme protein can be made to "fly through the vapor phase" -- from which solvent water is totally absent -- without changing its structure.
When a solution containing the enzyme was introduced as a fine spray into a vacuum created in a mass spectrometer in the laboratory, normal solvent molecules were completely evaporated, leaving bare, charged molecules known as ions, the researchers said. The protein ions were trapped in the extremely high vacuum for seconds, but in the new experiments, a single water molecule remained undisturbed, which was a surprise since no one ever saw that before.
"This suggests how we might change an inhibitor molecule to make it fit the enzyme more perfectly and hence be more effective in blocking that enzyme's action in destroying anticancer drugs," said Dr. Richard V. Wolfenden, Alumni Distinguished professor of biochemistry and biophysics at the UNC School of Medicine.
The experiments involving the enzyme cytidine deaminase, which is derived from bacteria and many other sources, mark the first time that scientists have detected a water molecule inside a protein molecule by mass spectrometry, he said.
A report on the research appears in the latest issue of the Proceedings of the National Academy of Sciences. Besides Wolfenden, UNC participants include lead author Dr. Christoph H. Borchers, assistant professor of biochemistry and biophysics and faculty director of the UNC Michael Hooker Proteomics Core Facility, and doctoral student Gottfried K. Schroeder. Wolfenden and Borchers are members of UNC's Lineberger Comprehensive Cancer Center.
"When the active site of this enzyme binds to what is called t
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University of North Carolina at Chapel Hill