Dihydropteroate synthase (DHPS) (DHPS)

Plasmodium dihydropteroate synthase (DHPS) is a vital enzyme in the de novo folate biosynthesis pathway of malaria-causing parasites, such as Plasmodium falciparum (UniProt: P13922). Unlike human hosts who obtain folate through dietary intake, Plasmodium parasites must synthesize folate to produce essential precursors for DNA synthesis and cellular replication (PubMed: 25131206). DHPS catalyzes the condensation of 6-hydroxymethyl-7,8-dihydropteridine pyrophosphate with p-aminobenzoic acid (PABA) to form 7,8-dihydropteroate. This enzyme is the primary target for sulfonamide drugs, including sulfadoxine and sulfamethoxazole, which act as structural analogs of PABA to competitively inhibit the enzyme (PubChem: CID 5307). However, the efficacy of these treatments is severely challenged by the emergence of point mutations in the dhps gene, such as A437G and K540E, which confer resistance by reducing drug binding affinity (PubMed: 30254005). Monitoring these genetic markers is essential for public health surveillance and the implementation of intermittent preventive treatment strategies.

Other names

7,8-dihydropteroate synthaseDihydropteroate pyrophosphorylaseHPPK-DHPSHydroxymethyldihydropterin pyrophosphokinase-dihydropteroate synthaseDihydropteroate synthase domain-containing protein

Sulfonamides and sulfones act as competitive inhibitors of the enzyme dihydropteroate synthase (DHPS). They are structural analogs of p-aminobenzoic acid (PABA) and compete for the PABA-binding site, thereby preventing the synthesis of dihydropteroate, a precursor of folic acid (PubMed: 25131206).