Dihydropteroate synthase (Mycobacterium leprae) (DHPS)

Dihydropteroate synthase (DHPS) is an essential enzyme in the folate biosynthesis pathway of Mycobacterium leprae, the bacterium responsible for leprosy. It catalyzes the condensation of para-aminobenzoic acid (PABA) with 6-hydroxymethyl-7,8-dihydropteridine pyrophosphate to form 7,8-dihydropteroate [UniProt: P0C0X1]. This process is critical for the production of tetrahydrofolate, which serves as a necessary cofactor for the synthesis of nucleic acids and proteins in the pathogen [PubMed: 10852355]. Because humans lack DHPS and obtain folate through dietary sources, the enzyme is a selective target for sulfonamide-class drugs and sulfones like dapsone [DrugBank: DB00250]. Dapsone acts as a structural analog of PABA, competitively inhibiting DHPS and leading to bacteriostatic effects [PubMed: 11518592]. Clinical resistance to dapsone is primarily mediated by specific mutations in the folP1 gene, which encodes the DHPS enzyme, particularly at positions 53 and 55 [WHO: Leprosy Resistance]. Consequently, DHPS remains a focal point for diagnostic resistance testing and the development of multidrug therapy regimens to treat Hansen's disease [PubMed: 12654734].

Other names

7,8-dihydropteroate synthasefolP1 proteinDihydropteroate pyrophosphorylaseDHPS

Competitive inhibition of para-aminobenzoic acid (PABA) binding to the enzyme, which prevents the formation of 7,8-dihydropteroate and subsequent folate synthesis.