Dihydropteroate synthase 2 (DHPS2)

Dihydropteroate synthase 2 (DHPS2) is an enzyme encoded by the folP2 gene (ML2095) in Mycobacterium leprae, the causative agent of leprosy (UniProt: Q9CB91). It is a structural homolog of DHPS1 (folP1), the primary enzyme in the folate biosynthesis pathway that catalyzes the condensation of para-aminobenzoic acid (PABA) with dihydropteridine pyrophosphate (PubMed: 10448246). While DHPS1 is the well-established therapeutic target for dapsone and sulfonamides, DHPS2 is often characterized as a non-functional paralog or pseudogene in M. leprae, as mutations conferring dapsone resistance are found exclusively in folP1 (PubMed: 10629311). Despite its lack of primary catalytic importance in clinical resistance, DHPS2 is studied to understand the evolution of the folate pathway and to ensure the specificity of molecular diagnostic tools (PubMed: 11118172). The enzyme belongs to the transferase family and is theoretically involved in the production of dihydrofolate, a precursor for DNA synthesis (NCBI: Gene ID 907056). Targeting the folate pathway remains a cornerstone of multidrug therapy (MDT) for leprosy, making the distinction between these two enzymes vital for molecular diagnostics and drug development.

Other names

folP2ML2095Dihydropteroate synthase II7,8-dihydropteroate synthase 2

Competitive inhibition of para-aminobenzoic acid (PABA) binding within the folate biosynthesis pathway, thereby preventing the synthesis of dihydrofolic acid (PubMed: 10448246).