Modification of near active site residues in organophosphorous hydrolase reduces metal stoichiometry and alters substrate specificity

The replacement of histidine by leucine at amino acid position 257 and by arginine at position 254 of the dimeric bacterial enzyme organophosphorous hydrolase (OPH) resulted in the creation of three altered enzymes. The resultant changes in substrate specificity upon the application of the enzymes to analogues of chemical warfare agents VX and soman, proves that OPH's specificity can be substantially enhanced through site-specific changes. It is also suggested that metal requirement modifications can affect catalytic attributes.