Stereochemical specificity of organophosphorus acid anhydrolase toward p-nitrophenyl analogs of soman and sarin

Organophosphorus acid anhydrolase (OPAA) catalyzes the hydrolysis of p-nitr ophenyl analogs of the organophosphonate nerve agents, sarin and soman. The enzyme is stereoselective toward the chiral phosphorus center by displayin g a preference for the R-p-configuration of these analogs. OPAA also exhibi ts an additional preference for the stereochemical configuration at the chi ral carbon center of the soman analog. The preferred configuration of the c hiral carbon center is dependent upon the configuration at the phosphorus c enter. The enzyme displays a two- to four-fold preference for the R-p-enant iomer of the sarin analog. The k(cat)/K-m of the R-p-enantiomer is 250 M-1 s(-1), while that of the S-p-enantiomer is 110 M-1 s(-1). The order of pref erence for the stereoisomers of the soman analog is RpSC > RpRC > SpRC > Sp SC. The k(cat)/K-m values are 36,300 M-1 s(-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 the refore preferred by a factor of 7000 over the SpSC-isomer. (C) 2001 Academi c Press.