Review Article

Organophosphorus Nerve Agents: Types, Toxicity, and Treatments

Table 1

List of mutants of organophosphatase and their activity in comparison to the wild-type enzymes.

EnzymesMutantsKcatKmKcat/KmActivity compared to WTReferences

PON1 3SRE, 1V04His115Trp 4HHO7.3 ± 0.2 s−11.6 ± 0.1 mM4700 ± 246 M−1s−1Increase in organophosphatase activity (paraoxonase activity)[127]

PON13B3 (Asn41Asp, Ser110Pro, Leu2240Ser, His243Arg, Phe264Leu, Asn324Asp, Thr332Ala)Not detectable (P(−)-CMP coumarin)Not detectable (P(−)-CMP-coumarin)<0.0002(1) μM−1 (P(−)-CMP-coumarin)Approx. 250-fold increase in catalytic efficiency[128130]

PON13D8 (Leu69Gly, His115Trp, His134Arg, Met196Val, Phe222Ser, Thr332Ser)546 ± 29 min−1 (P(−)-CMP-coumarin)36.7 ± 7 μM (P(−)-CMP-coumarin)12.7 ± 2 (>63,000) μ−1min−1 (P (−)-CMP-coumarin)A similar rate of hydrolysis for P (+) and P(−) isomers[130]

PTEGWT-f5 (His254Gly/His257Trp/Leu303Thr/Met317Leu/Ile106Cys/Phe132Ile/Leu271Ile/Lys185Arg/Ile274Asn/Ala80Val/Arg67His) 3URB1.2 × 102 s−1 (analogues of cyclosarin P(−))3.2 × 105 M−1s−1 (analogues of cyclosarin P(−))Best mutant for hydrolysis of cyclosarin analogues[75]

PTEL7eP-3a-I106G (His245Gln/His257Phe/Ile106Cys/Phe132Val/Ser308Leu/His257Tyr/Ala270Val/Leu272Met/Ile274Asn/Ile106Gly) 4ZSU58 s−1 (P(+)-APVR), 166 s−1 (P(−)-APVR), 545 s−1 (paraoxon) not detectable (DEVX)0.71 mM (P (+)-APVR), 0.31 mM (P(−)-APVR), 33 μM (paraoxon) not detectable (DEVX)8.2 × 10⁴ M−1s−1 (P (+)-APVR), 5.3 × 105 M−1s−1 (P(−)-APVR), 1.67 × 107 M−1s−1 (paraoxon), 7.7 × 103 M−1s−1 (DEVX)620-fold increase in catalytic activity for P (−)-VR type agents[131]

PTEHis254Gly/His257Trp/Leu303ThrIncreased in turnover no. by 3 orders for a toxic isomer of soman[132]

DFPaseSer271Ala30% increase in enzymatic activity for DFP[133]

DFPase 1PJXHis287Phe,14 s−10.03 ± 0.005 mMIncrease in activity for DFP[134]

PTE-like lactonase 3FDKTry28Leu/Asp71Asn/Tyr97Phe/Glu101Gly/Glu179Asp/V235Leu/Pro274Leu 4J356.8 × 104 s−13.6 × 105 M−1s−1Enhanced activity with methyl phosphonates[76]

OPH 1DPMHis254Arg, His257Leu640 s−1 (paraoxon), 50 s−1 (demeton-S)0.07 ± 0.01 mM (paraoxon), 6.2 ± 1.4 mM (demeton-S)9.14 × 106 M−1s−1 (paraoxon), 8.06 × 10³ M−1s−1 (demeton-S)Increased catalytic activity for VX and VR[135]

OPH 1DPMHis254Arg 1QW7750 s−1 (paraoxon)0.012 mM (paraoxon)6.25 × 107 M−1s−1 (paraoxon)11.3-fold increase in activity[136]

OPH22A11 (Ala14Thr, Ala80Val,Lys185Arg, H257Y, Ile274Asn)39600 ± 2100 s·s−1 (methyl parathion)0.62 ± 0.02 mM (methyl parathion)6.4 × 107 M−1s−1 (methyl parathion)25-fold increase activity for methyl parathion[137]

OPHLeu27Ile/Try309Ala0.15 s−15.87 mM24.9 M·s−1150-fold increase activity for VXa[138]

ProlidaseTyr301Cys/Lys342Asn2861 s−12.92 ± 0.40 mM980 mM−1s−1Thermostable and increase activity for soman[139]

OPAAFL (Try212Phe/Val342Leu)6.9 × 104 ± 3 × 103 min−1 (GP), 6.6 × 104 ± 3.4 × 103 min−1 (soman), 4.52 × 104 ± 4.62 × 103 min−1 (sarin)534.924 ± 67.8 μM (GP), 883.16 ± 156.4 μM (soman), 5.31 × 103 ± 1 × 103μM (sarin)1.29 × 108 ± 2.21 × 107 M−1min−1 (GP), 7.48 × 107 ± 1.71 × 107 M−1min−1 (soman), 8.50 × 106 ± 2.49 × 106 M−1min−1 (sarin)Increase in catalysis compared to wild type and preference to R (+) enantiomer of sarin[140]