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Sterochemical probes of enzyme-catalyzed phosphotransfer reactions

Thesis/Dissertation ·
OSTI ID:6898756

Enzyme-catalyzed phospho group transfer reactions are of fundamental importance in biological systems. One of the primary goals of research on the reaction mechanisms of these enzymes is to distinguish between a double displacement pathway involving a phospho-enzyme intermediate and a single displacement pathway involving direct transfer of the phospho group with a ternary complex. The distinction between these two pathways has relied upon a number of experimental techniques, including the detection of a phospho-enzyme intermediate, the demonstration of partial exchange reactions, and the elucidation of the steady-state kinetic behavior. A more direct probe of the reaction mechanism, however, involves the determination of the stereochemical course of the reaction at phosphorus. The stereochemical approach has been used to determine the course of the several displacements at phosphorus catalyzed by the enzymes phosphoenolpyruvate synthetase and pyruvate, orthophosphate dikinase. First, 2-((R)-/sup 16/O, /sup 17/O, /sup 18/O)Phospho-d-glycerate has been synthesized and used to determine the stereochemical fate of the ..beta..-phospho group of ATP in these enzyme-catalyzed reactions. Secondly, adenosine 5'-O-(..gamma..S)-..beta gamma..-/sup 17/O,..gamma..-/sup 17/O, /sup 18/O)(3-thiotriphosphate) has been synthesized and used to determine the stereochemical fate of the ..gamma..-phospho group of ATP. A method for the analysis of the absolute configuration at phosphorus in D-fructose 2,6-(2-/sup 16/O,/sup 17/O,/sup 18/O)biphosphate has been developed.

Research Organization:
Harvard Univ., Boston, MA (USA)
OSTI ID:
6898756
Country of Publication:
United States
Language:
English