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Literature summary for 2.5.1.15 extracted from

  • Satuluri, S.H.; Katari, S.K.; Pasala, C.; Amineni, U.
    Novel and potent inhibitors for dihydropteroate synthase of Helicobacter pylori (2020), J. Recept. Signal Transduct. Res., 40, 246-256 .
    View publication on PubMed
Search for more literature for 2.5.1.15

Inhibitors

Inhibitors Comment Organism Structure
4-[[(2-amino-4-oxo-3,4-dihydropteridin-6-yl)methyl]amino]-N-(3,4-dimethyl-1,2-oxazol-5-yl)benzene-1-sulfonamide 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 showed 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 Helicobacter pylori
4-[[(2-amino-4-oxo-3,4-dihydropteridin-6-yl)methyl]amino]-N-(3,4-dimethyl-1,2-oxazol-5-yl)benzene-1-sulfonamide
-
 Yersinia pestis

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
(7,8-dihydropterin-6-yl)methyl diphosphate + 4-aminobenzoate Yersinia pestis 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 diphosphate + 7,8-dihydropteroate
-
 ?
(7,8-dihydropterin-6-yl)methyl diphosphate + 4-aminobenzoate Helicobacter pylori 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 diphosphate + 7,8-dihydropteroate
-
 ?
(7,8-dihydropterin-6-yl)methyl diphosphate + 4-aminobenzoate Helicobacter pylori SNT49 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 diphosphate + 7,8-dihydropteroate
-
 ?

Organism

Organism UniProt Comment Textmining
Helicobacter pylori G2MFH6
-
-
Helicobacter pylori SNT49 G2MFH6
-
-
Yersinia pestis A0A384KP04
-
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
(7,8-dihydropterin-6-yl)methyl diphosphate + 4-aminobenzoate
-
 Yersinia pestis diphosphate + 7,8-dihydropteroate
-
 ?
(7,8-dihydropterin-6-yl)methyl diphosphate + 4-aminobenzoate
-
 Helicobacter pylori diphosphate + 7,8-dihydropteroate
-
 ?
(7,8-dihydropterin-6-yl)methyl diphosphate + 4-aminobenzoate 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 Yersinia pestis diphosphate + 7,8-dihydropteroate
-
 ?
(7,8-dihydropterin-6-yl)methyl diphosphate + 4-aminobenzoate 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 Helicobacter pylori diphosphate + 7,8-dihydropteroate
-
 ?
(7,8-dihydropterin-6-yl)methyl diphosphate + 4-aminobenzoate
-
 Helicobacter pylori SNT49 diphosphate + 7,8-dihydropteroate
-
 ?
(7,8-dihydropterin-6-yl)methyl diphosphate + 4-aminobenzoate 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 Helicobacter pylori SNT49 diphosphate + 7,8-dihydropteroate
-
 ?

General Information

General Information Comment Organism
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 Helicobacter pylori
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 Yersinia pestis
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 Helicobacter pylori