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Literature summary extracted from

  • Leite, F.H.A.; Froes, T.Q.; da Silva, S.G.; de Souza, E.I.M.; Vital-Fujii, D.G.; Trossini, G.H.G.; Pita, S.S.D.R.; Castilho, M.S.
    An integrated approach towards the discovery of novel non-nucleoside Leishmania major pteridine reductase 1 inhibitors (2017), Eur. J. Med. Chem., 132, 322-332 .
    View publication on PubMed

Application

EC Number Application Comment Organism
1.5.1.33 drug development the enzyme is considered a promising target for anti-leishmanial drug development and several inhibitors that share the substrate scaffold Leishmania major

Cloned(Commentary)

EC Number Cloned (Comment) Organism
1.5.1.33 gene PTR1, recombinant expression of His6-tagged enzyme in Escherichia coli strain BL21(DE3) Leishmania major

Inhibitors

EC Number Inhibitors Comment Organism Structure
1.5.1.33 (Z)-5-(2,4-dichlorobenzylidene)-thiazolidine-2,4-dione
-
 Leishmania major
1.5.1.33 (Z)-5-(2-bromo-5-methoxybenzylidene)-thiazolidine-2,4-dione
-
 Leishmania major
1.5.1.33 (Z)-5-(2-bromo-6-fluorobenzylidene)-thiazolidine-2,4-dione
-
 Leishmania major
1.5.1.33 (Z)-5-(2-hydroxy-3-bromo-5-chlorobenzylidene)-thiazolidine-2,4-dione a noncompetitive inhibitor that binds in the same site as the cofactor Leishmania major
1.5.1.33 (Z)-5-(2-hydroxy-5-chlorobenzylidene)-thiazolidine-2,4-dione
-
 Leishmania major
1.5.1.33 5-(3,4-dichlorobenzylidene)-thiazolidine-2,4-dione
-
 Leishmania major
1.5.1.33 additional information the enzyme is considered a promising target for anti-leishmanial drug development and several inhibitors that share the substrate scaffold. Design of a series of thiazolidine-2,4-dione derivatives as PTR1 inhibitors by employing the thiazolidinone ring as a bioisosteric replacement for pteridine/purine ring, docking studies, molecular dynamics simulations, and inhibition mechanism, overview Leishmania major

KM Value [mM]

EC Number KM Value [mM] KM Value Maximum [mM] Substrate Comment Organism Structure
1.5.1.33 additional information
-
 additional information kinetics, thermal shift assay Leishmania major

Natural Substrates/ Products (Substrates)

EC Number Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
1.5.1.33 biopterin + 2 NADPH + 2 H+ Leishmania major
-
 5,6,7,8-tetrahydrobiopterin + 2 NADP+
-
 ?

Organism

EC Number Organism UniProt Comment Textmining
1.5.1.33 Leishmania major
-
-
-

Reaction

EC Number Reaction Comment Organism Reaction ID
1.5.1.33 5,6,7,8-tetrahydrobiopterin + 2 NADP+ = biopterin + 2 NADPH + 2 H+ the enzyme exhhibits a ping-pong mechanism Leishmania major
a

Substrates and Products (Substrate)

EC Number Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
1.5.1.33 biopterin + 2 NADPH + 2 H+
-
 Leishmania major 5,6,7,8-tetrahydrobiopterin + 2 NADP+
-
 ?
1.5.1.33 additional information thermal shift enzyme assay optimization Leishmania major ?
-
 ?

Synonyms

EC Number Synonyms Comment Organism
1.5.1.33 pteridine reductase 1
-
 Leishmania major
1.5.1.33 PTR1
-
 Leishmania major

Temperature Optimum [°C]

EC Number Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
1.5.1.33 30
-
 assay at Leishmania major

Temperature Stability [°C]

EC Number Temperature Stability Minimum [°C] Temperature Stability Maximum [°C] Comment Organism
1.5.1.33 additional information
-
 midpoint temperatures of the LmPTR1-unfolding transition (Tm) at different pHs, DMSO concentrations, and inhibitor concentrations, thermal shift enzyme assay optimization, overview Leishmania major

pH Optimum

EC Number pH Optimum Minimum pH Optimum Maximum Comment Organism
1.5.1.33 4.7
-
 assay at Leishmania major

pH Stability

EC Number pH Stability pH Stability Maximum Comment Organism
1.5.1.33 4.5 7.5 enzyme LmPTR1 is stable either in pH 4.5 or pH 7.5, since Tm values does not vary significantly between these conditions Leishmania major

Cofactor

EC Number Cofactor Comment Organism Structure
1.5.1.33 NADPH
-
 Leishmania major

Ki Value [mM]

EC Number Ki Value [mM] Ki Value maximum [mM] Inhibitor Comment Organism Structure
1.5.1.33 additional information
-
 additional information inhibition kinetics, thermal shift assay Leishmania major