Dihydropteroate synthase, Plasmodium falciparum (DHPS (PfDHPS))

Dihydropteroate synthase (DHPS) is a critical enzyme in Plasmodium falciparum’s folate biosynthetic pathway, catalyzing the condensation of 6-hydroxymethyl-7,8-dihydropterin pyrophosphate with p-aminobenzoic acid (pABA) to form dihydropteroate, a precursor in tetrahydrofolate synthesis. The bifunctional enzyme, encoded by the PPPK-DHPS gene, frequently exhibits mutations in field isolates that confer resistance to sulfonamide drugs such as sulfadoxine, commonly used for malaria prophylaxis and treatment. These mutations alter substrate or drug binding at the enzyme’s active site, leading to therapeutic challenges. Monitoring dhps genotypes is essential for malaria control programs to track resistance and optimize antimalarial strategies[1][2][3][4][5][6].

Other names

DHPSPPPK-DHPS (when referring to the bifunctional enzyme form including 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase domain)Hydroxymethyldihydropterin pyrophosphokinase–dihydropteroate synthase

Drugs such as sulfadoxine act as competitive inhibitors of dihydropteroate synthase at the active site, blocking the incorporation of p-aminobenzoic acid (pABA) and preventing downstream tetrahydrofolate synthesis essential for DNA replication in P. falciparum[3][4][2].