Arabidopsis dihydropteroate synthase: general properties and inhibition by reaction product and sulfonamides.
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Prabhu V, Lui H, King J
Arabidopsis dihydropteroate synthase: general properties and inhibition by reaction product and sulfonamides.
Phytochemistry. 1997 May;45(1):23-7.
- PubMed ID
- 9127492 [ View in PubMed]
- Abstract
Dihydropteroate synthase (DHPS) (EC 2.5.1.15) was extracted from leaves of Arabidopsis thaliana and purified 21-fold by ion-exchange chromatography. This enzyme preparation was then characterized for several of its properties. Michaelis-Menten constants for the substrates, p-aminobenzoic acid and dihydropteridine diphosphate were estimated to be 2.5 and 91 microM, respectively. In an optimized assay, the reaction product, dihydropteroic acid, competitively inhibited the enzyme activity with a Ki of 81 microM. However, neither dihydropteroic acid nor tetrahydrofolate, products further downstream in the biosynthetic pathway inhibited enzymatic activity. This appears to be the first report of product inhibition of DHPS from a higher plant. The relative inhibitory properties of several sulfonamides, analogues of p-aminobenzoic acid, were also examined. The substitutions on the amide nitrogen of the sulfonamides influenced the degree of inhibition; thus I50 values for the inhibition of the DHPS activity by sulfanilamide, sulfacetamide and sulfadiazine were estimated to be 18.6, 9.6 and 4.2 microM, respectively. The competitive pattern of inhibition was shown in experiments with sulfadiazine.
DrugBank Data that Cites this Article
- Drug Targets
Drug Target Kind Organism Pharmacological Action Actions Sulfadiazine Dihydropteroate synthetase Protein Plasmodium falciparum YesInhibitorDetails Sulfamoxole Dihydropteroate synthetase Protein Plasmodium falciparum YesInhibitorDetails Sulfanilamide Dihydropteroate synthase Protein Escherichia coli (strain K12) YesInhibitorDetails