Dihydropteroate synthase

Dihydropteroate synthase 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) $\rightleftharpoons$ diphosphate + dihydropteroate.

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) Q46389 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 sulphonamides, which are substrate analogues that compete with para-aminobenzoic acid. Bacterial DHPS (gene sul or folP)^[1] 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 lower eukaryote Pneumocystis carinii, DHPS is the C-terminal domain of a multifunctional folate synthesis enzyme (gene fas).^[2]

References

↑ Crawford IP, Slock J, Stahly DP, Six EW, Han CY (1990). "An apparent Bacillus subtilis folic acid biosynthetic operon containing pab, an amphibolic trpG gene, a third gene required for synthesis of para-aminobenzoic acid, and the dihydropteroate synthase gene". J. Bacteriol. 172 (12): 7211–7226. PMC 210846. PMID 2123867.
↑ Volpe F, Dyer M, Scaife JG, Darby G, Stammers DK, Delves CJ (1992). "The multifunctional folic acid synthesis fas gene of Pneumocystis carinii appears to encode dihydropteroate synthase and hydroxymethyldihydropterin pyrophosphokinase". Gene 112 (2): 213–218. doi:10.1016/0378-1119(92)90378-3. PMID 1313386.

External links

Dihydropteroate synthetase at the US National Library of Medicine Medical Subject Headings (MeSH)

Metabolism of vitamins, coenzymes, and cofactors

Fat soluble vitamins

Vitamin A	Retinol binding protein

Vitamin E	Alpha-tocopherol transfer protein

Vitamin D	liver (Sterol 27-hydroxylase or CYP27A1) renal (25-Hydroxyvitamin D₃ 1-alpha-hydroxylase or CYP27B1) degradation (1,25-Dihydroxyvitamin D₃ 24-hydroxylase or CYP24A1)

Vitamin K	Vitamin K epoxide reductase

Water soluble vitamins

Thiamine (B₁)

Thiamine diphosphokinase

Niacin (B₃)

Pantothenic acid (B₅)

Pantothenate kinase

Folic acid (B₉)

Dihydropteroate synthase Dihydrofolate reductase Serine hydroxymethyltransferase

Methylenetetrahydrofolate reductase

Vitamin B₁₂

Vitamin C

L-gulonolactone oxidase

Riboflavin (B₂)

Riboflavin kinase

Nonvitamin cofactors

Tetrahydrobiopterin

GTP cyclohydrolase I 6-pyruvoyltetrahydropterin synthase Sepiapterin reductase

PCBD1 PTS QDPR

Molybdenum cofactor

Transferases: alkyl and aryl (EC 2.5)

2.5.1	Dimethylallyltranstransferase Thiaminase I Methionine adenosyltransferase Riboflavin synthase Dihydropteroate synthase Spermidine synthase Glutathione S-transferase Farnesyl-diphosphate farnesyltransferase Spermine synthase Alkylglycerone phosphate synthase Farnesyltransferase Geranylgeranyltransferase type 1 Porphobilinogen deaminase

Proteins: enzymes

Activity	Active site Binding site Catalytic triad Oxyanion hole Enzyme promiscuity Catalytically perfect enzyme Coenzyme Cofactor Enzyme catalysis Enzyme kinetics Lineweaver–Burk plot Michaelis–Menten kinetics

Regulation	Allosteric regulation Cooperativity Enzyme inhibitor

Classification	EC number Enzyme superfamily Enzyme family List of enzymes

Types	EC1 Oxidoreductases(list) EC2 Transferases(list) EC3 Hydrolases(list) EC4 Lyases(list) EC5 Isomerases(list) EC6 Ligases(list)

This article incorporates text from the public domain Pfam and InterPro IPR000489

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