Dihydropteroate synthetase, which catalyzes the condensation of 2-amino-4-hydroxy-6-hydroxymethyldihydropteridine pyrophosphate and p-aminobenzoic acid to form dihydropteroic acid, has been isolated from cells of the rodent malarial organism Plasmodium berghei; some of its properties are described. The optimum pH for enzyme activity was found to be 8.5. The apparent Michaelis constants for p-aminobenzoic acid and the hydroxymethyldihydropteridine pyrophosphate were found to be 2.8 µM and 1.4 µM, respectively. Both 4,4'-diaminodiphenylsulfone (I50 = 89 µM) and sulfadiazine (I50 = 180 µM) were effective inhibitors of enzyme activity. The inhibition of the enzyme by these drugs correlated with their activity in vivo against P. berghei infections.
ACKNOWLEDGMENT The authors were greatly aided in the preparation of this paper by discussion with Dr. Betty P. Vogh.
- Copyright ©, 1974, by Academic Press, Inc.