TDR Targets

Detailed view for Tb927.8.2210

Basic information

TDR Targets ID: 14105
Trypanosoma brucei, pteridine reductase 1
Source Database / ID: TriTrypDB GeneDB

pI: 6.4808 | Length (AA): 268 | MW (Da): 28470 | Paralog Number: 0

Signal peptide: N | GPI Anchor: | Predicted trans-membrane segments: 0

Druggability Group : DG4

Targets have been classified into druggability groups (DG) according to their druggability score in network driven prioritizations. DGs range from 1 to 5; the higher the group number, the higher the chance of the target to be druggable

Network

Pfam domains

PF13561 Enoyl-(Acyl carrier protein) reductase

Gene Ontology

Mouse over links to read term descriptions.

GO:0005575 cellular_component
GO:0005488 binding
GO:0003824 catalytic activity
GO:0016491 oxidoreductase activity
GO:0008152 metabolic process

Metabolic Pathways

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

Structural information

Modbase 3D models:

No model available for this protein in Modbase.

PDB Structures:

2C7V:

Resolution	Method	# Atoms	# Residues	Dep. Date	Pub. Date	Mod. Date

2VZ0:

Resolution	Method	# Atoms	# Residues	Dep. Date	Pub. Date	Mod. Date

2WD7:

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2WD8:

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2X9G:

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2X9N:

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2X9V:

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2YHI:

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2YHU:

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3BMC:

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3BMD:

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3BME:

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3BMF:

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3BMG:

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3BMH:

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3BMI:

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3BMJ:

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3BMK:

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3BML:

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3BMM:

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3BMN:

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3BMO:

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3BMQ:

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3BMR:

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3GN1:

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3GN2:

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3JQ6:

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3JQ7:

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3JQ8:

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3JQ9:

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3JQA:

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3JQB:

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3JQC:

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3JQD:

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3JQE:

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3JQF:

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3JQG:

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3MCV:

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4CL8:

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4CLD:

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4CLE:

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4CLH:

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4CLO:

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4CLR:

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4CLX:

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4CM1:

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4CM3:

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4CM4:

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4CM5:

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4CM6:

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4CM7:

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4CM8:

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4CM9:

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4CMA:

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4CMB:

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4CMC:

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4CME:

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4CMG:

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4CMI:

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4CMJ:

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4CMK:

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4WCD:

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4WCF:

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5IZC:

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5JCJ:

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5JCX:

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5JDC:

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5JDI:

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5K6A:

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Expression

Upregulation Percent	Ranking	Stage	Dataset
Upper 80-100% percentile		Procyclic, Bloodstream Form.	Siegel TN

Show/Hide expression data references

Siegel TN

Genome-wide analysis of mRNA abundance in two life-cycle stages of Trypanosoma brucei and identification of splicing and polyadenylation sites.

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	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

Tb927.8.2210 has direct evidence of essentiality

Gene/Ortholog	Organism	Phenotype	Source Study
Tb927.8.2210 this record	Trypanosoma brucei	no significant loss or gain of fitness in bloodstream forms (3 days)	alsford
Tb927.8.2210 this record	Trypanosoma brucei	significant loss of fitness in bloodstream forms (6 days)	alsford
Tb927.8.2210 this record	Trypanosoma brucei	significant loss of fitness in procyclic forms	alsford
Tb927.8.2210 this record	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

keio

Systematic single-gene knock-out mutants of E. coli K12

The Keio Collection

nmpdr

Genome-scale essentiality datasets from published studies (M. tuberculosis)

National Microbial Pathogen Data Resource

gerdes

Experimental determination and system-level analysis of essential genes in E. coli MG1655

Gerdes et al., J Bacteriol. 2003 185:5673-84

wormbase

C. elegans RNAi experiments

WormBase web site, http://www.wormbase.org, release WS170

alsford

High-throughput phenotyping using parallel sequencing of RNA interference targets in the African trypanosome

Genome Res 2011, 21:915-924

yeastgenome

Systematic deletion of yeast genes

Saccharomyces Genome Database

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.

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.

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.

blattner

Systematic mutagenesis of the E. coli (MG1655) genome

J Bacteriol 2004, 186:4921-4930

neb

C. elegans RNAi phenotypes

Data obtained from Wormbase WS150, curated by K. Chaudary and T. Carlow, New England Biolabs

shigen

Profiling of E. coli Chromosome (PEC)

National Institute of Genetics, Japan

Phenotypes and Validation (curated)

Annotated phenotypes:

Affected Entity	Phenotypic quality	Occurs in	Occurs at	Evidence	Observed in	Drugs/Inhibitors
cell proliferation (GO:0008283)	normal (PATO:0000461)		bloodstream stage trypomastigotes (PLO:0027)	inferred from RNAi experiment (ECO:0000019)		No drug identifiers listed for this gene.
Annotator:	fernan@iib.unsam.edu.ar.	Comment:	normal cell proliferation (no significant loss or gain of fitness) in bloodstream forms (stage 3 days).		References:	21363968
cell proliferation (GO:0008283)	decreased (PATO:0000468)		bloodstream stage trypomastigotes (PLO:0027)	inferred from RNAi experiment (ECO:0000019)		No drug identifiers listed for this gene.
Annotator:	fernan@iib.unsam.edu.ar.	Comment:	decreased cell proliferation (significant loss of fitness) in bloodstream forms (stage 6 days).		References:	21363968
cell proliferation (GO:0008283)	decreased (PATO:0000468)		procyclic (PLO:0034)	inferred from RNAi experiment (ECO:0000019)		No drug identifiers listed for this gene.
Annotator:	fernan@iib.unsam.edu.ar.	Comment:	decreased cell proliferation (significant loss of fitness) in procyclic forms .		References:	21363968
cell proliferation (GO:0008283)	normal (PATO:0000461)		procyclic (PLO:0034)	inferred from RNAi experiment (ECO:0000019)		No drug identifiers listed for this gene.
Annotator:	fernan@iib.unsam.edu.ar.	Comment:	normal cell proliferation (no significant loss or gain of fitness) in differentiation of procyclic to bloodstream forms .		References:	21363968

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.

In any case, if you have information about papers containing relevant validation data for this target, please contact us.

Annotated validation

Validation: inhibited in cell-free system. As observed in: T. b. brucei.Evidence: inferred from specific protein inhibition
annotated by: ts4@sanger.ac.uk.
References: 16968221

Associated compounds / Druggability

Druggability index (range: 0 to 1): 0.7

Known modulators for this target

Compound	Source	Reference
	ChEMBL23	References
	ChEMBL23	References
	ChEMBL23	References
	ChEMBL23	References
	ChEMBL23	References
	Curated by TDRTargets	References
	Curated by TDRTargets	References
	Curated by TDRTargets	References
	Curated by TDRTargets	References
	Curated by TDRTargets	References
	Curated by TDRTargets	References
	ChEMBL23	References

Predicted associations

By orthology with druggable targets

Species	Known druggable target	Linked compounds	Reference
Leishmania major	pteridine reductase 1	Compounds	References

By sequence similarity to non orthologous druggable targets

Species	Target	Length	Identity	Alignment span	Linked Drugs	Reference
Staphylococcus aureus subsp. aureus MRSA252	Enoyl-[acyl-carrier-protein] reductase	256 aa	24.3%	276 aa	Compounds	References
Staphylococcus aureus	Enoyl-ACP reductase	243 aa	24.5%	269 aa	Compounds	References
Staphylococcus aureus	Enoyl-[acyl-carrier-protein] reductase [NADPH]	256 aa	24.3%	276 aa	Compounds	References
Staphylococcus aureus (strain NCTC 8325)	Enoyl-[acyl-carrier-protein] reductase [NADPH] FabI	256 aa	24.3%	276 aa	Compounds	References
Bacillus subtilis (strain 168)	Enoyl-[acyl-carrier-protein] reductase [NADH]	258 aa	24.8%	282 aa	Compounds	References
Francisella tularensis subsp. tularensis (strain SCHU S4 / Schu 4)	Enoyl-[acyl-carrier-protein] reductase [NADH]	260 aa	23.0%	265 aa	Compounds	References

Ranking Plot

Putative Drugs List

Raw	Global	Species
0.0235	0.9866	1
0.0208	0.9832	1
0.0235	0.8832	1
0.0199	0.8311	1
0.0795	0.5078	0.5072
0.0624	0.9931	1
0.0205	0.6691	1
0.0202	0.8675	0.8445
0.0364	0.7733	1
0.0205	0.9862	1
0.0214	0.254	1
0.0235	0.8311	1
0.0121	0.3455	1
0.0191	0.2671	1
0.0448	0.9933	1
0.0235	0.4722	1
0.0295	0.9924	1
0.0488	0.9933	1
0.0568	0.9945	1
0.0198	0.2847	1
0.0271	0.2902	1
0.0795	0.5078	0.5072
0.0293	1	1
0.0026	0.3431	0
0.0235	0.2833	1
0.0832	0.5896	1
0.0283	0.962	0.5
0.0303272	0.995036	1
0.0888	1	1
0.0649	0.7187	0.7187
0.0249526	0.634676	0.882476
0.0411	0.9862	1
0.0235	0.9832	1
0.0256	0.3131	0
0.0289	0.8975	0.8921
0.0613	1	1
0.0579	0.5566	1
0.0235	0.2662	1
0.059	0.5976	1
0.1094	1	1
0.0235	0.7552	0.8901
0.1013	0.9591	1
0.0184	0.9309	0.9309
0.0407	0.9813	0.5
0.1207	0.9867	1
0.056	0.9936	1
0.0402	0.3934	0
0.0235	0.542	1
0.0611	0.2514	1
0.1057	0.4473	1
0.0666	1	1
0.021	0.8716	0
0.0208	0.6665	1
0.0201	0.9001	1
0.032	0.9923	1
0.1054	0.5409	1
0.013	0.8847	0.8746
0.0649	0.7187	0.7187
0.0235	0.5125	1
0.0599	0.4372	1
0.0491	0.9933	1
0.0076	0.3786	0.8413
0.0207	0.8311	1
0.0254357	0.995733	0.5
0.0544	0.6765	1
0.0196	0.2902	1
0.0295	0.8958	0.8908
0.0211	0.4851	0.4851
0.0133	0.8786	0.8782
0.0235	0.9843	0.5
0.0235	0.3406	0.7748
0.0389	0.985	1
0.0243	0.9572	0.9458
0.0235	0.6266	0.6266
0.0491	0.9933	1
0.0342	0.5722	1
0.062	1	1
0.0192	0.281	1
0.0543	0.4862	1
0.0284	0.5668	1
0.0345	1	1
0.0254357	0.995733	0.5
0.0857	0.9866	1
0.0214	0.2555	1
0.0352	0.3735	1
0.0627	0.7633	1
0.0352	0.9819	1
0.0193	0.2996	1
0.0256	0.3131	0
0.0422	0.9862	1
0.2646	0.2685	0.507
0.0235	0.9862	1
0.0588	1	1
0.0223	0.7904	0.9214
0.3593	0.2987	0.5608
0.0311	0.3667	1
0.065	0.4132	1
0.041	0.3443	0
0.0599	0.4372	1
0.0635	0.8435	1
0.0195	0.3622	1
0.0235	0.4304	1
0.0411	0.9862	1
0.0795	0.5078	0.5072
0.0206	0.8692	1
0.0235	0.2833	1
0.0235	0.5304	1
0.0303272	0.995782	1
0.0339	0.4142	1
0.0235	0.9832	1
0.058	0.9933	1
0.0235	0.2738	1
0.0227	0.3314	0.7707
0.0196	0.4144	1
0.0201	0.9832	1
0.0235	0.7552	0.8901
0.3593	0.2987	0.5608
0.0303272	0.384706	0.379482
0.0235	0.9862	1
0.0568	0.2817	1
0.058	0.9862	1
0.058	0.9933	1
0.0287	1	1
0.0192	0.3413	0
0.0235	0.2871	1
0.0339	0.5604	1
0.0795	0.5078	0.5072
0.0643	0.8508	1
0.0293	1	1
0.0788	0.9934	1
0.0806	0.992	1
0.0621	0.9934	1
0.0301	0.3901	1
0.0188	0.9863	1
0.0607	0.7946	1
0.019	0.3057	1
0.0193	0.4824	1
0.0594	1	1
0.0783	0.9938	1
0.0414	0.266	0.3304
0.0582	1	1

Assayability

Assay information

ChEMBL
Apparent inhibition of Trypanosoma brucei pteridine reductase 1-mediated reduction of cytochrome c
ChEMBL
Inhibition of Trypanosoma brucei pteridine reductase 1 at 100 uM

Reagent availability

No reagent availability information for this target.

Bibliographic References

1 literature reference was collected for this gene.

If you have references for this gene, please enter them in a user comment (below) or Contact us.

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Gene identifier	Tb927.8.2210 (Trypanosoma brucei), pteridine reductase 1

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