Increased VX and G-Agent Activity of Various Phosphotriesterase Enzyme Mutants

摘要

Seven different site-directed mutants of the phosphotriesterase (PTE) enzyme were constructed and assayed to determine their activity on VX, soman, and sarin. Two of these mutants (H254A and 11O6A/F1 32A/H257Y) had VX activity approximately three times and eleven times greater respectively, than the wild- type PTE enzyme. Several mutants were also found to possess increased levels of activity towards sarin and soman, including two (116A/H257Y and 11O6A/F132A/ h257Y) that possessed the highest levels of sarin yet reported for any enzyme. Stereochemical studies were conducted using PTE, mutant PTE enzymes and organophosphate acid anhydrolase (OPAA) enzymes with GF as a substrate.