PROSITE documentation PDOC00630

Dihydropteroate synthase signatures

All organisms require reduced folate cofactors for the synthesis of a variety of metabolites. Most microorganisms must synthesize folate de novo because they lack the active transport system of higher vertebrate cells which allows these organisms to use dietary folates. Enzymes that are involved in the biosynthesis of folates are therefore the target of a variety of antimicrobial agents such as trimethoprim or sulfonamides.

Dihydropteroate synthase (EC 2.5.1.15) (DHPS) catalyzes the condensation of 6-hydroxymethyl-7,8-dihydropteridine pyrophosphate to para-aminobenzoic acid to form 7,8-dihydropteroate. This is the second step in the three steps pathway leading from 6-hydroxymethyl-7,8-dihydropterin to 7,8-dihydrofolate. DHPS is the target of sulfonamides which are substrates analog that compete with para-aminobenzoic acid.

Bacterial DHPS (gene sul or folP) [1] is a protein of about 275 to 315 amino acid residues which is either chromosomally encoded or found on various antibiotic resistance plasmids. In the lower eukaryote Pneumocystis carinii, DHPS is the C-terminal domain of a multifunctional folate synthesis enzyme (gene fas) [2].

We developed two signature patterns for DHPS, the first signature is located in the N-terminal section of these enzymes, while the second signature is located in the central section.