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Literature summary extracted from

  • Rao, G.S.; Kumar, M.
    Structure-based design of a potent and selective small peptide inhibitor of Mycobacterium tuberculosis 6-hydroxymethyl-7, 8-dihydropteroate synthase: a computer modelling approach (2008), Chem. Biol. Drug Des., 71, 540-545.
    View publication on PubMed

Application

EC Number Application Comment Organism
2.5.1.15 drug development lead compound for design of antimicrobacterial inhibitors Mycobacterium tuberculosis

Crystallization (Commentary)

EC Number Crystallization (Comment) Organism
2.5.1.15 structure-based molecular modelling of the missing loop 2 (PDB: 1EYE) using Escherichia coli DHPS (PDB: 1AJZ) for further docking approaches, (i) extraction and docking of pterin monophosphate (PtP), KD(PtP): 0.5 microM, (ii) ternary complex of dapson docked with enzyme-PtP complex, KD(dapson): 0.2 microM, contacts with residues S53, R54, P55, F182, K213, (iii) ternary complex of pteroic acid (PTA) docked with enzyme-PtP complex, contacts with pterin- and 4-aminobenzoate-binding regions, (iv) inhibitor complex with dipeptide Trp-Lys (WK), contacts with residues E51, S53, D21, D86, K213, R253, and four water molecules, KD(WK): 0.23 nM Mycobacterium tuberculosis

Inhibitors

EC Number Inhibitors Comment Organism Structure
2.5.1.15 dapson KD: 0.2 microM according to molecular modelling Mycobacterium tuberculosis
2.5.1.15 Pteroic acid PTA, product analog, binds pterin- and 4-aminobenzoate-binding regions Mycobacterium tuberculosis
2.5.1.15 Trp-Lys WK, highly potent with KD: 0.23 nM according to structure-based molecular modelling and docking, overlaps with pterin monophosphate and pteroic acid binding regions, highly selective for microbial DHPS compared to human pterin and folate-binding enzymes (dihydrofolate reductase, thymidylate synthase) Mycobacterium tuberculosis

Natural Substrates/ Products (Substrates)

EC Number Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
2.5.1.15 4-aminobenzoate + (2-amino-4-hydroxy-7,8-dihydropteridin-6-yl)methyl diphosphate Mycobacterium tuberculosis
-
 diphosphate + 7,8-dihydropteroate
-
 ?
2.5.1.15 4-aminobenzoate + (2-amino-4-hydroxy-7,8-dihydropteridin-6-yl)methyl diphosphate Mycobacterium tuberculosis H37Rv
-
 diphosphate + 7,8-dihydropteroate
-
 ?

Organism

EC Number Organism UniProt Comment Textmining
2.5.1.15 Mycobacterium tuberculosis P9WND1
-
-
2.5.1.15 Mycobacterium tuberculosis H37Rv P9WND1
-
-

Substrates and Products (Substrate)

EC Number Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
2.5.1.15 4-aminobenzoate + (2-amino-4-hydroxy-7,8-dihydropteridin-6-yl)methyl diphosphate
-
 Mycobacterium tuberculosis diphosphate + 7,8-dihydropteroate
-
 ?
2.5.1.15 4-aminobenzoate + (2-amino-4-hydroxy-7,8-dihydropteridin-6-yl)methyl diphosphate
-
 Mycobacterium tuberculosis H37Rv diphosphate + 7,8-dihydropteroate
-
 ?

Synonyms

EC Number Synonyms Comment Organism
2.5.1.15 6-hydroxymethyl-7,8-dihydropteroate synthase
-
 Mycobacterium tuberculosis
2.5.1.15 DHPS
-
 Mycobacterium tuberculosis