Human paraoxonase double mutants hydrolyze V and G class organophosphorus nerve agents

► Human PON1 mutants were produced to improve OP binding at lower concentrations. ► F347W/H115W GB hydrolysis was achieved by a KM which was nearly half H115W alone. ► Stereoselective hydrolysis was improved for the P(-) isomer of GA in variant F347W/H115W. ► VX hydrolysis was unaltered by mutations.