Dihydropteroate synthase

Dihydropteroate synthase (DHPS) is an enzyme classified under EC 2.5.1.15. It produces dihydropteroate in bacteria, but it is not expressed in most eukaryotes including humans. This makes it a useful target for sulfonamide antibiotics, which compete with the PABA precursor.

• (2-amino-4-hydroxy-7,8-dihydropteridin-6-yl)methyl diphosphate + 4-aminobenzoate (PABA) ${\displaystyle \rightleftharpoons }$ diphosphate + dihydropteroate.

Dihydropteroate synthetase
Tetrahydrofolate synthesis pathway
Identifiers
EC no.	2.5.1.15
CAS no.	9055-61-2
Databases
IntEnz	IntEnz view
BRENDA	BRENDA entry
ExPASy	NiceZyme view
KEGG	KEGG entry
MetaCyc	metabolic pathway
PRIAM	profile
PDB structures	RCSB PDB PDBe PDBsum
Gene Ontology	AmiGO / QuickGO
Search PMC articles PubMed articles NCBI proteins

Pterin binding enzyme
Identifiers
Symbol	Pterin_bind
Pfam	PF00809
InterPro	IPR000489
PROSITE	PDOC00630
SCOP2	1ajz / SCOPe / SUPFAM
Available protein structures: Pfam   structures / ECOD   PDB RCSB PDB; PDBe; PDBj PDBsum structure summary PDB 1twzA:28-230 1twsA:28-230 1twwB:28-230 1tx0A:28-230 1tx2A:28-230 1ad1B:9-210 1ad4A:9-210 1eyeA:11-220 1ajz :20-228 1aj2 :20-228 1aj0 :20-228 2bmbA:509-774 1q8aB:315-515 1q7zB:315-515 1q85A:315-515 1q8jA:315-515 1q7qB:315-515 1q7mA:315-515 1f6yA:1-206

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 that allows these organisms to use dietary folates. Proteins containing this domain include dihydropteroate synthase (EC 2.5.1.15) as well as a group of methyltransferase enzymes including methyltetrahydrofolate, corrinoid iron-sulphur protein methyltransferase (MeTr)^[1] that catalyses a key step in the Wood-Ljungdahl pathway of carbon dioxide fixation.

Dihydropteroate synthase (EC 2.5.1.15) (DHPS) catalyses 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-step pathway leading from 6-hydroxymethyl-7,8-dihydropterin to 7,8-dihydrofolate. DHPS is the target of sulfonamides, which are substrate analogues that compete with para-aminobenzoic acid. Bacterial DHPS (gene sul or folP)^[2] is a protein of about 275 to 315 amino acid residues that is either chromosomally encoded or found on various antibiotic resistance plasmids. In the fungus Pneumocystis jirovecii (previously P. carinii) DHPS is the C-terminal domain of a multifunctional folate synthesis enzyme (gene fas).^[3]