EC Number   |
General Information |
Reference |
|---|
    2.5.1.15 | drug target |
dihydropteroate synthase is the target of the sulfonamide class of drugs |
759244 |
| 2.5.1.15 | drug target |
drug-resistant strains of Helicobacter pylori and multitudinous drug reactions are obstacles in the treatment of Helicobacter pylori infections a reliable tertiary structure of dihydropteroate synthase in complex with inhibitor 4-[[(2-amino-4-oxo-3,4-dihydropteridin-6-yl)methyl]amino]-N-(3,4-dimethyl-1,2-oxazol-5-yl)benzene-1-sulfonamide is constructed by Modeler 9v19. DrugBank compounds of DHPS, published inhibitors, and co-crystal ligand (4-[[(2-amino-4-oxo-3,4-dihydropteridin-6-yl)methyl]amino]-N-(3,4-dimethyl-1,2-oxazol-5-yl)benzene-1-sulfonamide) are docked against dihydropteroate synthase. The best docked compounds are screened against 28.5 million compounds result 1186 structural analogs. Virtual screening workflow and quantum polarized ligand dockings of these compounds against dihydropteroate synthase result three leads that show better XP Gscores, ADME properties, and binding-free energies compared to 4-[[(2-amino-4-oxo-3,4-dihydropteridin-6-yl)methyl]amino]-N-(3,4-dimethyl-1,2-oxazol-5-yl)benzene-1-sulfonamide, DrugBank compounds, and published inhibitors. The proposed leads are also validated by receiver operative characteristic (ROC) curve metrics in the presence of thousand decoys and the best docked existing compounds against DHPS. Long-range molecular dynamics (MD) simulations for 100 ns are executed after post-docking evaluations. Trajectory analysis shows that inter-molecular interactions of the lead-dihydropteroate synthase docking complex are stable throughout the entire runtime of MD simulations than 6MB-DHPS complex and Eliglustat-DHPS complex. The study outcomes show good competitive binding propensity and active-tunneling of leads over the existing inhibitors, thereby these leads could be ideal inhibitors against dihydropteroate synthase to target Helicobacter pylori |
-, 759674 |
| 2.5.1.15 | drug target |
target for anti-malarial and anti-bacterial drugs |
759889 |
| 2.5.1.15 | drug target |
the enzyme is a sulfa drug target in malaria treatment |
758651 |
| 2.5.1.15 | drug target |
the enzyme is target of drugs like sulfadoxine (SDX). The SDX effectiveness as an antimalarial drug is increasingly diminished by the rise and spread of drug-resistant mutations |
-, 759490 |
| 2.5.1.15 | evolution |
dihydropteroate synthase is a key enzyme in the folate pathway of bacteria and primitive eukaryotes |
723771 |
| 2.5.1.15 | malfunction |
prevalence and frequency of the dihydropteroate synthetase mutations associated with sulfadoxine-pyrimethamine resistance in southern Mozambique are examined between 1999 and 2004. The dihydropteroate synthetase double mutation frequency peaks in 2001 but declines to baseline levels by 2004. Parasites with both dihydrofolate reductase triple and dihydropteroate synthetase double mutations increase in 2001 but decrease by 2004. The peaking of sulfadoxine-pyrimethamine resistance markers in 2001 coincides with a sulfadoxine-pyrimethamine-resistant malaria epidemic in neighboring KwaZulu-Natal, South Africa. The decline in dihydropteroate synthetase (but not dihydrofolate reductase) mutations correspond with replacement of sulfadoxine-pyrimethamine with artemether-lumefantrine as malaria treatment policy in KwaZulu-Natal |
684380 |
| 2.5.1.15 | metabolism |
dihydropteroate synthase is a key enzyme in the folate pathway of bacteria and primitive eukaryotes |
723771 |
| 2.5.1.15 | metabolism |
reactions in the folate biosynthetic pathway |
-, 759490 |
| 2.5.1.15 | metabolism |
the enzyme catalyzes the condensation between (7,8-dihydropterin-6-yl)methyl diphosphate and 4-aminobenzoate to produce 7,8-dihydropteroate, a precursor of tetrahydrofolate. It plays a great role in folate synthesis pathway essential for amino acids biosynthesis |
-, 759674 |
