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Literature summary for 2.5.1.15 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

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

Crystallization (Commentary)

Crystallization (Comment) Organism
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

Inhibitors Comment Organism Structure
dapson KD: 0.2 microM according to molecular modelling Mycobacterium tuberculosis
Pteroic acid PTA, product analog, binds pterin- and 4-aminobenzoate-binding regions Mycobacterium tuberculosis
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)

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

Organism

Organism UniProt Comment Textmining
Mycobacterium tuberculosis P9WND1
-
-
Mycobacterium tuberculosis H37Rv P9WND1
-
-

Substrates and Products (Substrate)

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

Synonyms

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