Toxoplasma gondii dihydropteroate synthase (DHPS) (DHPS)

Toxoplasma gondii dihydropteroate synthase (DHPS) is an essential enzyme in the folate biosynthetic pathway of the protozoan parasite Toxoplasma gondii [UniProt]. It catalyzes the formation of 7,8-dihydropteroate from p-aminobenzoic acid (PABA) and 6-hydroxymethyl-7,8-dihydropterin pyrophosphate [UniProt]. This step is vital for the production of tetrahydrofolate, a necessary cofactor for the synthesis of nucleic acids and amino acids [PubChem]. Since humans lack the de novo folate synthesis pathway and instead rely on dietary folate, DHPS is a highly selective target for antimicrobial therapy [CDC]. Sulfonamide drugs, such as sulfadiazine, act as competitive inhibitors of DHPS by mimicking the substrate PABA [PubChem]. Inhibition of this enzyme leads to the depletion of folate pools, effectively arresting the growth and replication of the parasite [CDC]. Clinical challenges include the development of resistance due to point mutations in the DHPS gene, particularly at codons 407 and 408, and the potential for severe allergic reactions to sulfonamides in some patients [PubMed, CDC].

Other names

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

Competitive inhibition of dihydropteroate synthase by acting as a p-aminobenzoic acid (PABA) analog [PubChem]