Stereochemical Specificity of Organophosphorus Acid Anhydrolase toward p-Nitrophenyl Analogs of Soman and Sarin

Abstract

Organophosphorus acid anhydrolase (OPAA) catalyzes the hydrolysis of p-nitrophenyl analogs of the organophosphonate nerve agents, sarin and soman. The enzyme is stereoselective toward the chiral phosphorus center by displaying a preference for the RP-configuration of these analogs. OPAA also exhibits an additional preference for the stereochemical configuration at the chiral carbon center of the soman analog. The preferred configuration of the chiral carbon center is dependent upon the configuration at the phosphorus center. The enzyme displays a two- to four-fold preference for the RP-enantiomer of the sarin analog. The kcat/Km of the RP-enantiomer is 250 M−1 s−1, while that of the SP-enantiomer is 110 M−1 s−1. The order of preference for the stereoisomers of the soman analog is RPSC >RPRC >SPRC >SPSC. The kcat/Km values are 36,300 M−1s−1, 1250 M−1 s−1, 80 M−1 s−1 and 5 M−1 s−1, respectively. The RPSC-isomer of the soman analog is therefore preferred by a factor of 7000 over the SPSC-isomer.