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Literature summary for 1.5.1.33 extracted from

  • Kumar, P.; Kumar, A.; Verma, S.S.; Dwivedi, N.; Singh, N.; Siddiqi, M.I.; Tripathi, R.P.; Dube, A.; Singh, N.
    Leishmania donovani pteridine reductase 1: biochemical properties and structure-modeling studies (2008), Exp. Parasitol., 120, 73-79.
    View publication on PubMed

Application

Application Comment Organism
drug development target for antifolate chemotherapy against Leishmania Leishmania donovani

Cloned(Commentary)

Cloned (Comment) Organism
expression of GFP-tagged enzyme in Leishmania donovani Leishmania donovani

Inhibitors

Inhibitors Comment Organism Structure
(4-fluoro-phenyl)-6-methyl-2-thioxo-1,2,3,4-tetrahydro-pyrimidine-5-carboxylic acid ethyl ester
-
Leishmania donovani
2,6-dimethyl [3-O-benzyl-1,2-O isopropylidene-beta-L-threo-pentofuronose-4-yl]-1-phenyl-1,4-dihydro pyridine-3,5-dicarboxylic acid diethyl ether
-
Leishmania donovani
sodium antimony gluconate
-
Leishmania donovani

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
2 biopterin + 3 NADPH + 3 H+ Leishmania donovani salvage of pterins, enzyme acts as a metabolic bypass for drugs targeting dihydrofolate reductase, PTR1 contributes about 10% of the reduction of folates in wild-type cells while the remaining 90% is due to the activity of dihydrofolate reductase-thymidylate synthase (EC 1.5.1.3) dihydrobiopterin + tetrahydrobiopterin + 3 NADP+
-
?
folate + NADPH + H+ Leishmania donovani
-
7,8-dihydrofolate + tetrahydrofolate + NADP+
-
?

Organism

Organism UniProt Comment Textmining
Leishmania donovani
-
clinical isolate
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
2 biopterin + 3 NADPH + 3 H+ salvage of pterins, enzyme acts as a metabolic bypass for drugs targeting dihydrofolate reductase, PTR1 contributes about 10% of the reduction of folates in wild-type cells while the remaining 90% is due to the activity of dihydrofolate reductase-thymidylate synthase (EC 1.5.1.3) Leishmania donovani dihydrobiopterin + tetrahydrobiopterin + 3 NADP+
-
?
folate + NADPH + H+
-
Leishmania donovani 7,8-dihydrofolate + tetrahydrofolate + NADP+
-
?

Synonyms

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

Cofactor

Cofactor Comment Organism Structure
NADPH
-
Leishmania donovani

IC50 Value

IC50 Value IC50 Value Maximum Comment Organism Inhibitor Structure
12.1
-
amastigote Leishmania donovani sodium antimony gluconate
18.3
-
amastigote Leishmania donovani 2,6-dimethyl [3-O-benzyl-1,2-O isopropylidene-beta-L-threo-pentofuronose-4-yl]-1-phenyl-1,4-dihydro pyridine-3,5-dicarboxylic acid diethyl ether
23.1
-
amastigote Leishmania donovani (4-fluoro-phenyl)-6-methyl-2-thioxo-1,2,3,4-tetrahydro-pyrimidine-5-carboxylic acid ethyl ester
90.8
-
promastigote Leishmania donovani 2,6-dimethyl [3-O-benzyl-1,2-O isopropylidene-beta-L-threo-pentofuronose-4-yl]-1-phenyl-1,4-dihydro pyridine-3,5-dicarboxylic acid diethyl ether
101
-
promastigote Leishmania donovani (4-fluoro-phenyl)-6-methyl-2-thioxo-1,2,3,4-tetrahydro-pyrimidine-5-carboxylic acid ethyl ester