Protein
Dihydropteroate synthase
Organism
Mycobacterium tuberculosis (strain CDC 1551 / Oshkosh)
Function
Is involved in the bioactivation of the antituberculous drug para-aminosalicylic acid (PAS). PAS is a close structural analog of pABA and acts as an alternative substrate for DHPS, leading to hydroxy-dihydropteroate (H2PtePAS). Metabolomic studies show that PAS, despite its in vitro activity as a competitive inhibitor of DHPS, does not inhibit growth of M.tuberculosis by inhibiting DHPS. PAS exerts its antimycobacterial activity through its effects on M.tuberculosis folate metabolism downstream of DHPS. PAS poisons folate-dependent pathways not only by serving as a replacement substrate for DHPS but also by the products of that reaction serving as replacement substrates and/or inhibitors of subsequent enzymes.
Similarity
Belongs to the DHPS family.
Sequence
MSPAPVQVMGVLNVTDDSFSDGGCYLDLDDAVKHGLAMAAAGAGIVDVGGESSRPGATRVDPAVETSRVIPVVKELAAQGITVSIDTMRADVARAALQNGAQMVNDVSGGRADPAMGPLLAEADVPWVLMHWRAVSADTPHVPVRYGNVVAEVRADLLASVADAVAAGVDPARLVLDPGLGFAKTAQHNWAILHALPELVATGIPVLVGASRKRFLGALLAGPDGVMRPTDGRDTATAVISALAALHGAWGVRVHDVRASVDAIKVVEAWMGAERIERDG