Detailed view for LmjF.23.0270

Basic information

TDR Targets ID: 21977
Leishmania major, pteridine reductase 1

Source Database / ID: TriTrypDB / LmjF.23.0270  GeneDB / LmjF.23.0270

pI: 7.115 | Length (AA): 288 | MW (Da): 30409 | Paralog Number: 0

Signal peptide: N | GPI Anchor: N | Predicted trans-membrane segments: ND

Pfam domains

PF00106   short chain dehydrogenase
PF13561   Enoyl-(Acyl carrier protein) reductase

Gene Ontology

Mouse over links to read term descriptions.
GO:0005488   binding  
GO:0003824   catalytic activity  
GO:0016491   oxidoreductase activity  
GO:0008152   metabolic process  

Network

Metabolic Pathways

This gene is not mapped to any metabolic pathway in KEGG.

Structural information

Modbase 3D models: 5

There are 5 models calculated for this protein. More info on these models, including the models themselves is available at: Modbase

Target Beg Target End Template Template Beg Template End Identity Evalue Model Score MPQS zDope
2 288 1nff (A) 3 243 29.00 0 1 1.14 -0.51
5 288 1e7w (A) 5 288 99.99 0 1 2.16 -1.46
2 78 1lu9 (A) 116 191 22.00 0.79 0.49 0.587361 -0.79
5 280 2xox (A) 5 280 93.00 0 1 1.75013 -0.43
5 288 1e7w (A) 5 288 99.99 0 1 2.09191 -0.77

Help me make sense of these data.

Target Beg: first modeled residue
Target End: last modeled residue
Template: template structure used for modelling (PDB accession and chain)
Template Beg: first template residue in target-template alignment
Template End: last template residue in target-template alignment
Identity: sequence identity
Evalue: E value for target-template hit
Model Score: GA341 score (>0.7 for reliable model)
MPQS: ModPipe Quality Score (>1.1 for reliable model)
zDope: zDope Score (negative for reliable model)

A more detailed description of these scores is available at the Modbase Model Evaluation Help Pages, and in the papers referenced therein.

PDB Structures:

  • 1E7W: One active site, two modes of reduction correlate the mechanism of leishmania pteridine reductase with pterin metabolism and antifolate drug resistance in trpanosomes
  • Gourley, D.G., Hunter, W.N.
  • Resolution Method # Atoms # Residues Dep. Date Pub. Date Mod. Date
    1.75 X-RAY DIFFRACTION 4108 582 2000-09-11 2001-09-06 2011-07-13
  • Ligand information
  • 1,2-ETHANEDIOL C(CO)O non-polymer Search in DB
  • METHOTREXATE CN(Cc1cnc2c(n1)c(nc(n2)N)N)c3ccc(cc3)C(=O)N[C@@H](CCC(=O)O)C(=O)O non-polymer Search in DB
  • NADPH DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE c1nc(c2c(n1)n(cn2)[C@H]3[C@@H]([C@@H]([C@H](O3)CO[P@](=O)(O)O[P@@](=O)(O)OC[C@@H]4[C@H]([C@H]([C@@H](O4)N5C=CCC(=C5)C(=O)N)O)O)O)OP(=O)(O)O)N non-polymer Search in DB
  • 1E92: Pteridine reductase 1 from Leishmania major complexed with NADP+ and dihydrobiopterin
  • Schuettelkopf, A.W., Hunter, W.N.
  • Resolution Method # Atoms # Residues Dep. Date Pub. Date Mod. Date
    2.20 X-RAY DIFFRACTION 8088 1152 2000-10-04 2001-10-05 2019-03-06
  • Ligand information
  • 1,2-ETHANEDIOL C(CO)O non-polymer Search in DB
  • 7,8-DIHYDROBIOPTERIN C[C@@H]([C@@H](C1=NC2=C(NC1)N=C(NC2=O)N)O)O non-polymer Search in DB
  • NADP NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE c1cc(c[n+](c1)[C@H]2[C@@H]([C@@H]([C@H](O2)CO[P@@](=O)([O-])O[P@](=O)(O)OC[C@@H]3[C@H]([C@H]([C@@H](O3)n4cnc5c4ncnc5N)OP(=O)(O)O)O)O)O)C(=O)N non-polymer Search in DB
  • 1W0C: Inhibition of Leishmania major pteridine reductase (PTR1) by 2,4,6-triaminoquinazoline; structure of the NADP ternary complex.
  • Mcluskey, K., Gibellini, F., Carvalho, P., Avery, M., Hunter, W.
  • Resolution Method # Atoms # Residues Dep. Date Pub. Date Mod. Date
    2.60 X-RAY DIFFRACTION 16341 2456 2004-06-02 2004-09-30 2011-07-13
  • Ligand information
  • NADP NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE c1cc(c[n+](c1)[C@H]2[C@@H]([C@@H]([C@H](O2)CO[P@@](=O)([O-])O[P@](=O)(O)OC[C@@H]3[C@H]([C@H]([C@@H](O3)n4cnc5c4ncnc5N)OP(=O)(O)O)O)O)O)C(=O)N non-polymer Search in DB
  • 2,4,6-TRIAMINOQUINAZOLINE c1cc2c(cc1N)c(nc(n2)N)N non-polymer Search in DB
  • 2BF7: Leishmania major pteridine reductase 1 in complex with NADP and biopterin
  • Schuettelkopf, A.W., Hunter, W.N.
  • Resolution Method # Atoms # Residues Dep. Date Pub. Date Mod. Date
    2.40 X-RAY DIFFRACTION 7991 1152 2004-12-06 2005-08-31 2019-03-06
  • Ligand information
  • 1,2-ETHANEDIOL C(CO)O non-polymer Search in DB
  • 7,8-DIHYDROBIOPTERIN C[C@@H]([C@@H](C1=NC2=C(NC1)N=C(NC2=O)N)O)O non-polymer Search in DB
  • NADP NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE c1cc(c[n+](c1)[C@H]2[C@@H]([C@@H]([C@H](O2)CO[P@@](=O)([O-])O[P@](=O)(O)OC[C@@H]3[C@H]([C@H]([C@@H](O3)n4cnc5c4ncnc5N)OP(=O)(O)O)O)O)O)C(=O)N non-polymer Search in DB
  • 2BFA: Leishmania major pteridine reductase 1 in complex with NADP and CB3717
  • Schuettelkopf, A.W., Hunter, W.N.
  • Resolution Method # Atoms # Residues Dep. Date Pub. Date Mod. Date
    2.70 X-RAY DIFFRACTION 8108 1152 2004-12-06 2005-08-31 2019-03-06
  • Ligand information
  • 10-PROPARGYL-5,8-DIDEAZAFOLIC ACID C#CCN(Cc1ccc2c(c1)C(=O)N=C(N2)N)c3ccc(cc3)C(=O)N[C@@H](CCC(=O)O)C(=O)O non-polymer Search in DB
  • 1,2-ETHANEDIOL C(CO)O non-polymer Search in DB
  • NADPH DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE c1nc(c2c(n1)n(cn2)[C@H]3[C@@H]([C@@H]([C@H](O3)CO[P@](=O)(O)O[P@@](=O)(O)OC[C@@H]4[C@H]([C@H]([C@@H](O4)N5C=CCC(=C5)C(=O)N)O)O)O)OP(=O)(O)O)N non-polymer Search in DB
  • 2BFM: Leishmania major pteridine reductase 1 in complex with NADP and trimethoprim
  • Schuettelkopf, A.W., Hunter, W.N.
  • Resolution Method # Atoms # Residues Dep. Date Pub. Date Mod. Date
    2.60 X-RAY DIFFRACTION 8003 1152 2004-12-09 2005-08-31 2019-03-06
  • Ligand information
  • NADPH DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE c1nc(c2c(n1)n(cn2)[C@H]3[C@@H]([C@@H]([C@H](O3)CO[P@](=O)(O)O[P@@](=O)(O)OC[C@@H]4[C@H]([C@H]([C@@H](O4)N5C=CCC(=C5)C(=O)N)O)O)O)OP(=O)(O)O)N non-polymer Search in DB
  • TRIMETHOPRIM COc1cc(cc(c1OC)OC)Cc2cnc(nc2N)N non-polymer Search in DB
  • 2BFO: Leishmania major pteridine reductase 1 in complex with NADPH
  • Schuettelkopf, A.W., Hunter, W.N.
  • Resolution Method # Atoms # Residues Dep. Date Pub. Date Mod. Date
    2.60 X-RAY DIFFRACTION 8003 1152 2004-12-10 2005-08-31 2019-03-06
  • Ligand information
  • 1,2-ETHANEDIOL C(CO)O non-polymer Search in DB
  • NADPH DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE c1nc(c2c(n1)n(cn2)[C@H]3[C@@H]([C@@H]([C@H](O3)CO[P@](=O)(O)O[P@@](=O)(O)OC[C@@H]4[C@H]([C@H]([C@@H](O4)N5C=CCC(=C5)C(=O)N)O)O)O)OP(=O)(O)O)N non-polymer Search in DB
  • 2BFP: Leishmania major pteridine reductase 1 in complex with NADP and tetrahydrobiopterin
  • Schuettelkopf, A.W., Hunter, W.N.
  • Resolution Method # Atoms # Residues Dep. Date Pub. Date Mod. Date
    2.55 X-RAY DIFFRACTION 8083 1152 2004-12-10 2005-08-31 2019-03-06
  • Ligand information
  • 1,2-ETHANEDIOL C(CO)O non-polymer Search in DB
  • 5,6,7,8-TETRAHYDROBIOPTERIN C[C@@H]([C@@H]([C@H]1CNC2=C(N1)C(=O)NC(=N2)N)O)O non-polymer Search in DB
  • NADP NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE c1cc(c[n+](c1)[C@H]2[C@@H]([C@@H]([C@H](O2)CO[P@@](=O)([O-])O[P@](=O)(O)OC[C@@H]3[C@H]([C@H]([C@@H](O3)n4cnc5c4ncnc5N)OP(=O)(O)O)O)O)O)C(=O)N non-polymer Search in DB
  • 2P8K: Selective screening and design to identify inhibitors of Leishmania major pteridine reductase 1.
  • Mcluskey, K., Gibellini, F., Hunter, W.N.
  • Resolution Method # Atoms # Residues Dep. Date Pub. Date Mod. Date
    2.40 X-RAY DIFFRACTION 16532 2304 2007-03-22 2007-12-25 2009-05-05
  • 2QHX: Structure of Pteridine Reductase from Leishmania major complexed with a ligand
  • Gibellini, F., Mcluskey, K., Tulloch, L., Hunter, W.N.
  • Resolution Method # Atoms # Residues Dep. Date Pub. Date Mod. Date
    2.61 X-RAY DIFFRACTION 8179 1312 2007-07-03 2007-12-25 2011-07-13
  • Ligand information
  • METHYL 1-(4-{[(2,4-DIAMINOPTERIDIN-6-YL)METHYL](METHYL)AMINO}BENZOYL)PIPERIDINE-4-CARBOXYLATE CN(Cc1cnc2c(n1)c(nc(n2)N)N)c3ccc(cc3)C(=O)N4CCC(CC4)C(=O)OC non-polymer Search in DB
  • IODIDE ION [I-] non-polymer Search in DB
  • NADP NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE c1cc(c[n+](c1)[C@H]2[C@@H]([C@@H]([C@H](O2)CO[P@@](=O)([O-])O[P@](=O)(O)OC[C@@H]3[C@H]([C@H]([C@@H](O3)n4cnc5c4ncnc5N)OP(=O)(O)O)O)O)O)C(=O)N non-polymer Search in DB
  • 3H4V: Selective screening and design to identify inhibitors of leishmania major pteridine reductase 1
  • Mcluskey, K., Gibellini, F., Hunter, W.N.
  • Resolution Method # Atoms # Residues Dep. Date Pub. Date Mod. Date
    2.40 X-RAY DIFFRACTION 16540 2304 2009-04-21 2009-05-05 2017-11-01
  • Ligand information
  • METHYL 1-(4-{[(2,4-DIAMINOPTERIDIN-6-YL)METHYL]AMINO}BENZOYL)PIPERIDINE-4-CARBOXYLATE COC(=O)C1CCN(CC1)C(=O)c2ccc(cc2)NCc3cnc4c(n3)c(nc(n4)N)N non-polymer Search in DB
  • NADP NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE c1cc(c[n+](c1)[C@H]2[C@@H]([C@@H]([C@H](O2)CO[P@@](=O)([O-])O[P@](=O)(O)OC[C@@H]3[C@H]([C@H]([C@@H](O3)n4cnc5c4ncnc5N)OP(=O)(O)O)O)O)O)C(=O)N non-polymer Search in DB
  • 5L42: Leishmania major Pteridine reductase 1 (PTR1) in complex with compound 3
  • Dello Iacono, L., Di Pisa, F., Pozzi, C., Landi, G., Mangani, S.
  • Resolution Method # Atoms # Residues Dep. Date Pub. Date Mod. Date
    2.10 X-RAY DIFFRACTION 8169 1152 2016-05-24 2017-05-03 2017-09-27
  • Ligand information
  • (2~{R})-2-[3,4-bis(oxidanyl)phenyl]-6-oxidanyl-2,3-dihydrochromen-4-one c1cc(c(cc1[C@H]2CC(=O)c3cc(ccc3O2)O)O)O non-polymer Search in DB
  • ACETATE ION CC(=O)[O-] non-polymer Search in DB
  • S-OXY CYSTEINE C([C@@H](C(=O)O)N)[S@H]=O L-peptide linking Search in DB
  • 1,2-ETHANEDIOL C(CO)O non-polymer Search in DB
  • GLYCEROL C(C(CO)O)O non-polymer Search in DB
  • NADPH DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE c1nc(c2c(n1)n(cn2)[C@H]3[C@@H]([C@@H]([C@H](O3)CO[P@](=O)(O)O[P@@](=O)(O)OC[C@@H]4[C@H]([C@H]([C@@H](O4)N5C=CCC(=C5)C(=O)N)O)O)O)OP(=O)(O)O)N non-polymer Search in DB
  • TRIETHYLENE GLYCOL C(COCCOCCO)O non-polymer Search in DB
  • 5L4N: Leishmania major Pteridine reductase 1 (PTR1) in complex with compound 1
  • Dello Iacono, L., Di Pisa, F., Pozzi, C., Landi, G., Mangani, S.
  • Resolution Method # Atoms # Residues Dep. Date Pub. Date Mod. Date
    2.35 X-RAY DIFFRACTION 8005 1152 2016-05-26 2017-03-22 2017-03-29
  • Ligand information
  • (2~{R})-2-(3-hydroxyphenyl)-6-oxidanyl-2,3-dihydrochromen-4-one c1cc(cc(c1)O)[C@H]2CC(=O)c3cc(ccc3O2)O non-polymer Search in DB
  • ACETATE ION CC(=O)[O-] non-polymer Search in DB
  • S-OXY CYSTEINE C([C@@H](C(=O)O)N)[S@H]=O L-peptide linking Search in DB
  • 1,2-ETHANEDIOL C(CO)O non-polymer Search in DB
  • GLYCEROL C(C(CO)O)O non-polymer Search in DB
  • NADPH DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE c1nc(c2c(n1)n(cn2)[C@H]3[C@@H]([C@@H]([C@H](O3)CO[P@](=O)(O)O[P@@](=O)(O)OC[C@@H]4[C@H]([C@H]([C@@H](O4)N5C=CCC(=C5)C(=O)N)O)O)O)OP(=O)(O)O)N non-polymer Search in DB
  • DI(HYDROXYETHYL)ETHER C(COCCO)O non-polymer Search in DB
  • TRIETHYLENE GLYCOL C(COCCOCCO)O non-polymer Search in DB

Expression

No expression data available for this gene

Orthologs

Ortholog group members (OG5_133937)
Species Accession Gene Product
Caenorhabditis elegans CELE_R05D8.10   Protein DHS-15
Escherichia coli b2137   putative oxidoreductase
Escherichia coli b1606   dihydromonapterin reductase, NADPH-dependent
Homo sapiens 728635   dehydrogenase/reductase (SDR family) member 4 like 1
Leishmania braziliensis LbrM.23.0300   pteridine reductase 1
Leishmania donovani LdBPK_230310.1   pteridine reductase 1
Leishmania infantum LinJ.23.0310   pteridine reductase 1
Leishmania major LmjF.23.0270 this record   pteridine reductase 1
Leishmania mexicana LmxM.23.0270   pteridine reductase 1
Trypanosoma brucei Tb927.8.2210   pteridine reductase 1
Trypanosoma congolense TcIL3000_8_2210   pteridine reductase 1

Essentiality

LmjF.23.0270 has one or more orthologs with essentiality data
Gene/Ortholog Organism Phenotype Source Study
Tb927.8.2210 Trypanosoma brucei no significant loss or gain of fitness in bloodstream forms (3 days) alsford
Tb927.8.2210 Trypanosoma brucei significant loss of fitness in bloodstream forms (6 days) alsford
Tb927.8.2210 Trypanosoma brucei significant loss of fitness in procyclic forms alsford
Tb927.8.2210 Trypanosoma brucei no significant loss or gain of fitness in differentiation of procyclic to bloodstream forms alsford
b1606 Escherichia coli non-essential goodall
b2137 Escherichia coli non-essential goodall

Show/Hide essentiality data references
  • gerdes Experimental determination and system-level analysis of essential genes in E. coli MG1655 Gerdes et al., J Bacteriol. 2003 185:5673-84
  • blattner Systematic mutagenesis of the E. coli (MG1655) genome J Bacteriol 2004, 186:4921-4930
  • keio Systematic single-gene knock-out mutants of E. coli K12 The Keio Collection
  • neb C. elegans RNAi phenotypes Data obtained from Wormbase WS150, curated by K. Chaudary and T. Carlow, New England Biolabs
  • sidik A Genome-wide CRISPR Screen in Toxoplasma Identifies Essential Apicomplexan Genes. Sidik, Saima M., et al. "A genome-wide CRISPR screen in toxoplasma identifies essential apicomplexan genes." Cell 166.6 (2016): 1423-1435.
  • alsford High-throughput phenotyping using parallel sequencing of RNA interference targets in the African trypanosome Genome Res 2011, 21:915-924
  • wormbase C. elegans RNAi experiments WormBase web site, http://www.wormbase.org, release WS170
  • goodall The Essential Genome of Escherichia coli K-12 (Transposon directed high-throughput mutagenesis) Goodall, Emily CA, et al. "The essential genome of Escherichia coli K-12." mBio 9.1 (2018): e02096-17.
  • yeastgenome Systematic deletion of yeast genes Saccharomyces Genome Database
  • shigen Profiling of E. coli Chromosome (PEC) National Institute of Genetics, Japan
  • nmpdr Genome-scale essentiality datasets from published studies (M. tuberculosis) National Microbial Pathogen Data Resource
  • plasmo Functional Profiling of a Plasmodium Genome Reveals an Abundance of Essential Genes. Bushell, Ellen, et al. "Functional profiling of a Plasmodium genome reveals an abundance of essential genes." Cell 170.2 (2017): 260-272.

Phenotypes and Validation (curated)

Annotated phenotypes:

Affected Entity Phenotypic quality Occurs in Occurs at Evidence Observed in Drugs/Inhibitors
growth (GO:0040007) drug sensitive (PATO:0000529) single cell organism (CARO:0000064) promastigote (BTO:0001124) inferred from loss-of-function mutant phenotype (ECO:0000016) Leishmania major 1763   48945   59943   547983   572016   572017  
Annotator: aaronjr@u.washington.edu. Comment: PTR1 null mutant leads to DHFR inhibitor sensitivity in promastigotes; successful inhibition of folate and pteridine metabolism will require complementary inhibition of DHFR and PTR1. References: 14981076 9153248
growth (GO:0040007) drug sensitive (PATO:0000529) single cell organism (CARO:0000064) promastigote (BTO:0001124) inferred from bioassay (ECO:0000094) Leishmania major 1763   48945   59943   547983   572016   572017  
Annotator: aaronjr@u.washington.edu. Comment: PTR1 null mutant leads to DHFR inhibitor sensitivity in promastigotes; successful inhibition of folate and pteridine metabolism will require complementary inhibition of DHFR and PTR1. References: 14981076 9153248
growth (GO:0040007) lethal (sensu genetics) (PATO:0000718) single cell organism (CARO:0000064) promastigote (BTO:0001124) inferred from loss-of-function mutant phenotype (ECO:0000016) Leishmania major No drug identifiers listed for this gene.
Annotator: aaronjr@u.washington.edu. Comment: PTR1 null mutant leads to cell death in promastigotes, unless culture medium is supplemented with certain pteridines; . References: 9153248
growth (GO:0040007) decreased time (PATO:0000716) single cell organism (CARO:0000064) promastigote (BTO:0001124) inferred from bioassay (ECO:0000094) Leishmania major 1669   1763   1855   8083   16294   26764   48945   59943   242358   247198   354733   419420   547983   558652   558653   561919   565286   565287   571120   571121   572016   572017   572304   573463  
Annotator: aaronjr@u.washington.edu. Comment: Drug: 700-47-0; Drug: 704-61-0; Drug: 708-74-7; Drug: 945-24-4; Drug: 1026-36-4; Drug: 1597-01-9; Drug: 1899-40-7; Drug: 2432-24-8; Drug: 2440-80-4; Drug: 3977-17-1; Drug: 5774-32-3; Drug: 6954-23-0; Drug: 6973-01-9; Drug: 7319-50-8; Drug: 14684-54-9; Drug: 17005-34-4; Drug: 17005-35-5; Drug: 19152-86-4; Drug: 26398-12-9; Drug: 34244-78-5; Drug: 34244-80-9; Drug: 36804-91-8; Drug: 38713-63-2; Drug: 38713-64-3; Drug: 38713-65-4; Drug: 47066-05-7; Drug: 50691-65-1; Drug: 51395-54-1; Drug: 51583-00-7; Drug: 52128-15-1; Drug: 53219-56-0; Drug: 53274-34-3; Drug: 54798-36-6; Drug: 58091-86-4; Drug: 61267-65-0; Drug: 61267-67-2; Drug: 73978-42-4; Drug: 73978-43-5; Drug: 73978-44-6; Drug: 89977-50-4; Drug: 104422-58-4; Drug: 104422-59-5; Drug: 107174-41-4; Drug: 160602-03-9; Drug: 160602-12-0; Drug: 200127-49-7; Drug: 200127-50-0; Drug: 200127-51-1; Drug: 200127-52-2; Drug: 200127-53-3; Drug: 200127-54-4; Drug: 200127-55-5; Drug: 200127-57-7; Drug: 200127-58-8; Drug: 200127-59-9; Drug: 200127-60-2; Drug: 200127-61-3; Drug: 200127-62-4; Drug: 200127-63-5. chemical inhibition with DHFR and PTR1 inhibitors leads to slow growth of Leishmania sp. in cell assay; . References: 9371081 9398595
catalytic activity (GO:0003824) decreased (PATO:0000468) in vitro (MI:0492) inferred from specific protein inhibition (ECO:0000020) Leishmania major 1669   1763   1855   8083   16294   26764   48945   59943   242358   247198   354733   419420   547983   558652   558653   561919   565286   565287   571120   571121   572016   572017   572304   573463  
Annotator: aaronjr@u.washington.edu. Comment: Drug: 700-47-0; Drug: 704-61-0; Drug: 708-74-7; Drug: 945-24-4; Drug: 1026-36-4; Drug: 1597-01-9; Drug: 1899-40-7; Drug: 2432-24-8; Drug: 2440-80-4; Drug: 3977-17-1; Drug: 5774-32-3; Drug: 6954-23-0; Drug: 6973-01-9; Drug: 7319-50-8; Drug: 14684-54-9; Drug: 17005-34-4; Drug: 17005-35-5; Drug: 19152-86-4; Drug: 26398-12-9; Drug: 34244-78-5; Drug: 34244-80-9; Drug: 36804-91-8; Drug: 38713-63-2; Drug: 38713-64-3; Drug: 38713-65-4; Drug: 47066-05-7; Drug: 50691-65-1; Drug: 51395-54-1; Drug: 51583-00-7; Drug: 52128-15-1; Drug: 53219-56-0; Drug: 53274-34-3; Drug: 54798-36-6; Drug: 58091-86-4; Drug: 61267-65-0; Drug: 61267-67-2; Drug: 73978-42-4; Drug: 73978-43-5; Drug: 73978-44-6; Drug: 89977-50-4; Drug: 104422-58-4; Drug: 104422-59-5; Drug: 107174-41-4; Drug: 160602-03-9; Drug: 160602-12-0; Drug: 200127-49-7; Drug: 200127-50-0; Drug: 200127-51-1; Drug: 200127-52-2; Drug: 200127-53-3; Drug: 200127-54-4; Drug: 200127-55-5; Drug: 200127-57-7; Drug: 200127-58-8; Drug: 200127-59-9; Drug: 200127-60-2; Drug: 200127-61-3; Drug: 200127-62-4; Drug: 200127-63-5. chemical inhibition with DHFR and PTR1 inhibitors leads to reduced enzyme activity in vitro; . References: 9371081 9398595
growth (GO:0040007) decreased time (PATO:0000716) single cell organism (CARO:0000064) amastigote (BTO:0000062) inferred from bioassay (ECO:0000094) Leishmania amazonensis 1855   587877  
Annotator: aaronjr@u.washington.edu. Comment: chemical inhibition with DHFR-PTR1 inhibitors leads to slow growth of Leishmania sp. in cell assay; . References: 14502550
catalytic activity (GO:0003824) decreased (PATO:0000468) in vitro (MI:0492) inferred from specific protein inhibition (ECO:0000020) Leishmania major No drug identifiers listed for this gene.
Annotator: aaronjr@u.washington.edu. Comment: Drug: 13741-90-7. chemical inhibition with PTR1 inhibitors leads to reduced enzyme activity in vitro; . References: 15388924

In TDR Targets, information about phenotypes that are caused by drugs, or by genetic manipulation of cells (e.g. gene knockouts or knockdowns) is manually curated from the literature. These descriptions help to describe the potential of the target for drug development. If no information is available for this gene or if the information is incomplete, this may mean that i) the papers containing this information either appeared after the curation effort for this organism was carried out or they were inadvertently missed by curators; or that ii) the curation effort for this organism has not yet started.
 
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Annotated validation

  • Validation: inhibited in cell-free system
  • annotated by: aaronjr@u.washington.edu.
  • References: 15388924 9371081 9398595
  • Validation: genetic disruption
  • annotated by: aaronjr@u.washington.edu.
  • References: 9153248

Associated compounds / Druggability

Druggability index (range: 0 to 1): 0.7

Curated from literature

55 chemical compounds are associated with this gene

Predicted associations

By orthology with druggable targets
Species Known druggable target Linked compounds Reference
Trypanosoma brucei pteridine reductase 1 Compounds References
By sequence similarity to non orthologous druggable targets
Species Target Length Identity Alignment span Linked Drugs Reference
Homo sapiens hydroxysteroid (17-beta) dehydrogenase 10 252 aa 23.7% 278 aa Compounds References
Homo sapiens hydroxyprostaglandin dehydrogenase 15-(NAD) 266 aa 27.5% 222 aa Compounds References
Cochliobolus lunatus 17-beta-hydroxysteroid-dehydrogenase 270 aa 24.2% 293 aa Compounds References

Assayability

Assay information

  • ChEMBL
  • Inhibition of Leishmania major recombinant PTR1
  • ChEMBL
  • Inhibition of Leishmania major PTR1
  • ChEMBL
  • Inhibition of Leishmania major PTR1 by Lineweaver-Burk analysis
  • ChEMBL
  • Inhibition of pteridine reductase in Leishmania major promastigotes assessed as increase in pyrimethamine-induced growth inhibition by measuring parasite growth at 50 ug/mL
  • ChEMBL
  • Inhibition of Leishmania major PTR1 by spectrophotometric assay
  • ChEMBL
  • Binding affinity to Leishmania major pteridine reductase 1
  • BRENDA Assay
  • An enzyme with this EC number or name or sequence has been assayed in Leishmania tarentolae ( 3 )

Reagent availability

  • Reagent:
  • Target Type Source Notes
    LmjF.23.0270 purified protein BRENDA A protein with this EC number or name or sequence has been purified from Leishmania tarentolae ( 2 )

Bibliographic References

6 literature references were collected for this gene.

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User comments

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Gene identifier LmjF.23.0270 (Leishmania major), pteridine reductase 1
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