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Information on EC 1.5.1.33 - pteridine reductase and Organism(s) Leishmania tarentolae and UniProt Accession P42556

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EC Tree
     1 Oxidoreductases
         1.5 Acting on the CH-NH group of donors
             1.5.1 With NAD+ or NADP+ as acceptor
                1.5.1.33 pteridine reductase
IUBMB Comments
The enzyme from Leishmania (both amastigote and promastigote forms) catalyses the reduction by NADPH of folate and a wide variety of unconjugated pterins, including biopterin, to their tetrahydro forms. It also catalyses the reduction of 7,8-dihydropterins and 7,8-dihydrofolate to their tetrahydro forms. In contrast to EC 1.5.1.3 (dihydrofolate reductase) and EC 1.5.1.34 (6,7-dihydropteridine reductase), pteridine reductase will not catalyse the reduction of the quinonoid form of dihydrobiopterin. The enzyme is specific for NADPH; no activity has been detected with NADH. It also differs from EC 1.5.1.3 (dihydrofolate reductase) in being specific for the Si-face of NADPH.
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Leishmania tarentolae
UNIPROT: P42556
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Word Map
The taxonomic range for the selected organisms is: Leishmania tarentolae
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota
Synonyms
pteridine reductase, pteridine reductase 1, tbptr1, lmptr1, ldptr1, tb-pr, nadph-dihydropteridine reductase, pteridine reductase i, more
SYNONYM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
pteridine reductase
-
H region methotrexate resistance protein
-
-
-
-
NADPH-dihydropteridine reductase
-
-
-
-
pteridine reductase 1
-
-
-
-
PTR1
-
-
-
-
reductase, dihydropteridine (reduced nicotinamide adenine dinucleotide phosphate)
-
-
-
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
oxidation
-
-
-
-
reduction
-
-
-
-
PATHWAY SOURCE
PATHWAYS
SYSTEMATIC NAME
IUBMB Comments
5,6,7,8-tetrahydrobiopterin:NADP+ oxidoreductase
The enzyme from Leishmania (both amastigote and promastigote forms) catalyses the reduction by NADPH of folate and a wide variety of unconjugated pterins, including biopterin, to their tetrahydro forms. It also catalyses the reduction of 7,8-dihydropterins and 7,8-dihydrofolate to their tetrahydro forms. In contrast to EC 1.5.1.3 (dihydrofolate reductase) and EC 1.5.1.34 (6,7-dihydropteridine reductase), pteridine reductase will not catalyse the reduction of the quinonoid form of dihydrobiopterin. The enzyme is specific for NADPH; no activity has been detected with NADH. It also differs from EC 1.5.1.3 (dihydrofolate reductase) in being specific for the Si-face of NADPH.
CAS REGISTRY NUMBER
COMMENTARY hide
131384-61-7
-
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
Biopterin + NADPH
5,6,7,8-Tetrahydrobiopterin + NADP+
show the reaction diagram
2-step reaction via intermediate 7,8-dihydrobiopterin
-
-
?
Biopterin + NADPH
5,6,7,8-Tetrahydrobiopterin + NADP+
show the reaction diagram
-
-
-
-
?
Dihydrobiopterin + NADPH
?
show the reaction diagram
-
-
-
-
?
Dihydrofolate + NADPH
5,6,7,8-Tetrahydrofolate + NADP+
show the reaction diagram
-
-
-
?
Dihydroneopterin + NADPH
?
show the reaction diagram
-
-
-
-
?
dihydrosepiapterin + NADPH
?
show the reaction diagram
-
-
-
-
?
folate + NADPH
5,6,7,8-tetrahydrofolate + NADP+
show the reaction diagram
additional information
?
-
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
additional information
?
-
COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
NADPH
binding structure
NADPH
-
dependent on
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
methotrexate
binding structure
additional information
-
-
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0032 - 0.0109
biopterin
0.033
dihydrobiopterin
-
-
0.0067
dihydrofolate
-
recombinant enzyme, pH 6.0
0.0019 - 0.085
folate
0.00935 - 0.0169
NADPH
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.22 - 0.23
biopterin
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
6
-
biopterin as substrate
pH RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
4.5 - 7
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pH 4.5: about 50% of maximal activity, pH 7.0: about 30% of maximal activity with biopterin
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION?
PTR1_LEITA
289
0
30744
Swiss-Prot
other Location (Reliability: 5)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
116800
-
gel filtration
30000
-
4 * 30000, SDS-PAGE
31000
-
2 * 31000, SDS-PAGE
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
tetramer
structure analysis
tetramer
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
purified recombinant enzyme in binary complex with NADPH and in ternary complex with NADPH and methotrexate, 0.02 ml of protein solution containing 20 mg/ml protein, 20 mM Tris-HCl, pH 7.0, mixed with 0.01 ml of a solution containing 4 mM NADPH, 4 mM methotrexate on ice for 1 h, then mixed with 0.01 ml of reservoir solution containing 28% 1,4-butanediol, 12.5 mM cetyl trimethyl ammonium chloride and 100 mM HEPES, pH 7.0, 5 days, 14°C, X-ray diffraction structure determination and analysis of flash frozen crystals at 2.8 A resolution, molecular replacement technique
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
K199E
-
The mutant enzymes Y38D, Y195F, Y195W, and K199R are inactive even if they are purified as tetramers
Y175D
-
mutant enzyme Y175D shows properties similar to wild type enzyme. The mutant enzymes Y38D, Y195F, Y195W, and K199R are inactive even if they are purified as tetramers
Y195F
-
The mutant enzymes Y38D, Y195F, Y195W, and K199R are inactive even if they are purified as tetramers
Y195W
-
The mutant enzymes Y38D, Y195F, Y195W, and K199R are inactive even if they are purified as tetramers
Y38D
-
The mutant enzymes Y38D, Y195F, Y195W, and K199R are inactive even if they are purified as tetramers
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
recombinant enzyme from Escherichia coli
recombinant enzyme
-
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
expression in Escherichia coli
expression in Escherichia coli
-
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Nare, B.; Hardy, L.W.; Beverley, S.M.
The roles of pteridine reductase 1 and dihydrofolate reductase-thymidylate synthase in pteridine metabolism in the protozoan parasite Leishmania major
J. Biol. Chem.
272
13883-13891
1997
Leishmania major, Leishmania tarentolae
Manually annotated by BRENDA team
Leblanc, E.; Papadopoulou, B.; Bernatchez, C.; Ouellette, M.
Residues involved in co-factor and substrate binding of the short-chain dehydrogenase/reductase PTR1 producing methotrexate resistance in Leishmania
Eur. J. Biochem.
251
768-774
1998
Leishmania tarentolae
Manually annotated by BRENDA team
Wang, J.; Leblanc, E.; Chang, C.F.; Papadopoulou, B.; Bray, T.; Witheley, J.M.; Lin, S.X.; Quellette, M.
Pterin and folate reduction by the Leishmania tarentolae H locus short-chain dehydrogenase/reductase PTR1
Arch. Biochem. Biophys.
342
197-202
1997
Leishmania tarentolae
Manually annotated by BRENDA team
Zhao, H.; Bray, T.; Ouellette, M.; Zhao, M.; Ferre, R.A.; Matthews, D.; Whiteley, J.M.; Varughese, K.I.
Structure of pteridine reductase (PTR1) from Leishmania tarentolae
Acta Crystallogr. Sect. D
59
1539-1544
2003
Leishmania tarentolae (P42556), Leishmania tarentolae
Manually annotated by BRENDA team