Any feedback?
Please rate this page
(literature.php)
(0/150)

BRENDA support

Literature summary for 1.5.1.33 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
Search for more literature for 1.5.1.33

Application

Application Comment Organism
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)

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

Inhibitors

Inhibitors Comment Organism Structure
(Z)-5-(2,4-dichlorobenzylidene)-thiazolidine-2,4-dione
-
 Leishmania major
(Z)-5-(2-bromo-5-methoxybenzylidene)-thiazolidine-2,4-dione
-
 Leishmania major
(Z)-5-(2-bromo-6-fluorobenzylidene)-thiazolidine-2,4-dione
-
 Leishmania major
(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
(Z)-5-(2-hydroxy-5-chlorobenzylidene)-thiazolidine-2,4-dione
-
 Leishmania major
5-(3,4-dichlorobenzylidene)-thiazolidine-2,4-dione
-
 Leishmania major
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]

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

Natural Substrates/ Products (Substrates)

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

Organism

Organism UniProt Comment Textmining
Leishmania major
-
-
-

Reaction

Reaction Comment Organism Reaction ID
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)

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

Synonyms

Synonyms Comment Organism
pteridine reductase 1
-
 Leishmania major
PTR1
-
 Leishmania major

Temperature Optimum [°C]

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

Temperature Stability [°C]

Temperature Stability Minimum [°C] Temperature Stability Maximum [°C] Comment Organism
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

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

pH Stability

pH Stability pH Stability Maximum Comment Organism
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

Cofactor Comment Organism Structure
NADPH
-
 Leishmania major

Ki Value [mM]

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