Under this project, support will be provided for a scientist from Sri Lanka, Dr. Srianthie A. Deraniyagala, of the Department of Chemistry, University of Colombo, Sri Lanka, to work in the laboratory of Dr. Rex Pratt of Wesleyan University in Middletown, CT. The research, to be carried out jointly, will seek to study the interaction of bacterial enzymes with antibiotics that may decrease the latters' effectiveness. Specifically, a combination of secondary and solvent kinetic deuterium isotope effects will be employed to determine the structure of Beta-lactamase transition states and the extent of their stabilization through proton motion. Extension of the experiments to the bacterial DD-peptidase enzymes, the targets of Beta-lactam antibiotics, are also planned, to further delineate the differences between the Beta-lactamase and DD-peptidase active sites. A close comparison of the results with previously obtained results of the serine proteinases will be made, to clarify the mechanisms of catalysis employed by these enzymes. Scope: The project brings a young, bright researcher from Sri Lanka to participate in research with, and learn new experimental techniques, from a well established and experienced U.S. researcher who has extensive knowledge in the field. This is likely to benefit both scientists, and to encourage the expansion of similar work in Sri Lanka in the future.
