Dihydropteroate synthase (Toxoplasma gondii) (DHPS)

Dihydropteroate synthase (DHPS) is a vital enzyme in the de novo folate biosynthetic pathway of the protozoan parasite Toxoplasma gondii (UniProt: P42429). In this organism, DHPS is expressed as a bifunctional enzyme combined with dihydropterin pyrophosphokinase (DHPPK), facilitating the conversion of p-aminobenzoic acid (PABA) and dihydropterin pyrophosphate into dihydropteroate (PubMed: 18463226). This step is essential for the production of tetrahydrofolate, a cofactor required for the synthesis of nucleic acids and amino acids. Because humans lack the DHPS enzyme and rely on dietary folate, it is a primary target for sulfonamide antibiotics like sulfadiazine, which act as competitive inhibitors of PABA (PubMed: 22434755). The inhibition of DHPS effectively halts parasite replication by starving it of necessary folate derivatives. However, the clinical utility of targeting DHPS is increasingly threatened by the emergence of specific point mutations in the DHPS gene that confer resistance to sulfonamides, particularly in immunocompromised patients (PubMed: 11598061).

Other names

7,8-dihydropteroate synthaseDihydropteroate pyrophosphorylaseDHPPK-DHPSDihydropterin pyrophosphokinase-dihydropteroate synthase

Competitive inhibition of the enzyme by mimicking p-aminobenzoic acid (PABA), thereby blocking the synthesis of dihydropteroate, a precursor of folic acid.