Detailed view for PF3D7_0922900

Basic information

TDR Targets ID: 4904
Plasmodium falciparum, 3-oxoacyl-[acyl-carrier-protein] reductase
Source Database / ID:  PlasmoDB   |   GeneDB   |   MPMP

pI: 9.7027 | Length (AA): 301 | MW (Da): 33347 | Paralog Number: 0

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

Druggability Group : DG3

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

Pfam domains

PF13561   Enoyl-(Acyl carrier protein) reductase

Gene Ontology

Mouse over links to read term descriptions.
GO:0020011   apicoplast  
GO:0051287   NAD binding  
GO:0016491   oxidoreductase activity  
GO:0005488   binding  
GO:0004316   3-oxoacyl-[acyl-carrier-protein] reductase activity  
GO:0003824   catalytic activity  
GO:0055114   oxidation reduction  
GO:0008152   metabolic process  
GO:0006633   fatty acid biosynthetic process  

Structural information

Modbase 3D models:

There are 4 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
17 299 2et6 (A) 278 546 36.00 0 1 1.35 -0.64
51 301 2c07 (A) 54 304 99.99 0 1 1.99 -1.95
14 297 3lls (A) 178 448 34.00 0 1 1.18292 0.62
51 301 2c07 (A) 54 304 99.99 0 1 2.06969 -1.69

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:

PDB tag
  • 2C07:
  • Resolution Method # Atoms # Residues Dep. Date Pub. Date Mod. Date

Expression

Upregulation Percent Ranking Stage Dataset
Upper 80-100% percentile sporozoite, Oocyst, Sporozoite, Female Gametocyte. PlasmoDB Zanghi G Lasonder E
Upregulation Percent Ranking Stage Dataset
Lower 20-40% percentile intra-erythrocytic - 32 hs, early trophozoite, late trophozoite, Ring, Male Gametocyte. Otto TD PlasmoDB Zanghi G Lasonder E
Upregulation Percent Ranking Stage Dataset
Lower 0-20% percentile intra-erythrocytic - 0 hs, intra-erythrocytic - 8 hs, intra-erythrocytic - 16 hs, intra-erythrocytic - 24 hs, intra-erythrocytic - 40 hs, intra-erythrocytic - 48 hs. Otto TD
Show/Hide expression data references
  • Zanghi G A Specific PfEMP1 Is Expressed in P. falciparum Sporozoites and Plays a Role in Hepatocyte Infection.
  • PlasmoDB Data on upregulation of P. falciparum genes in different life cycle stages, combined from several microarray experiments available in PlasmoDB
  • Otto TD New insights into the blood-stage transcriptome of Plasmodium falciparum using RNA-Seq.
  • Lasonder E Integrated transcriptomic and proteomic analyses of P. falciparum gametocytes. Molecular insight into sex-specific processes and translational repression.

Orthologs

Ortholog group members (OG5_126618)

Species Accession Gene Product
Arabidopsis thaliana AT1G24360   3-oxoacyl-[acyl-carrier-protein] reductase
Brugia malayi Bm1_07940   oxidoreductase, short chain dehydrogenase/reductase family protein
Brugia malayi Bm1_48885   oxidoreductase, short chain dehydrogenase/reductase family protein
Candida albicans CaO19.10417   3-oxoacyl-(acyl carrier protein) reductase
Candida albicans CaO19.5763   similar to bacterial reductase
Candida albicans CaO19.2899   3-oxoacyl-(acyl carrier protein) reductase
Candida albicans CaO19.13186   short-chain alcohol dehydrogenase superfamily
Caenorhabditis elegans CELE_Y39A1A.11   Protein DHS-11
Caenorhabditis elegans CELE_F09E10.3   Protein DHS-25
Caenorhabditis elegans CELE_Y47G6A.22   Protein Y47G6A.22
Chlamydia trachomatis CT_237   oxoacy-ACP reductase
Dictyostelium discoideum DDB_G0269356   hypothetical protein
Dictyostelium discoideum DDB_G0283727   short-chain dehydrogenase/reductase family protein
Dictyostelium discoideum DDB_G0292602   hypothetical protein
Drosophila melanogaster Dmel_CG31546   CG31546 gene product from transcript CG31546-RA
Drosophila melanogaster Dmel_CG12171   CG12171 gene product from transcript CG12171-RA
Drosophila melanogaster Dmel_CG31549   CG31549 gene product from transcript CG31549-RA
Drosophila melanogaster Dmel_CG31548   CG31548 gene product from transcript CG31548-RA
Drosophila melanogaster Dmel_CG3603   CG3603 gene product from transcript CG3603-RB
Escherichia coli b1093   3-oxoacyl-[acyl-carrier-protein] reductase
Escherichia coli b2842   hexuronate dehydrogenase
Echinococcus granulosus EgrG_000792800   3 oxoacyl acyl carrier protein reductase
Entamoeba histolytica EHI_186920   3-oxoacyl-(acyl-carrier protein) reductase, putative
Echinococcus multilocularis EmuJ_000792800   3 oxoacyl acyl carrier protein reductase
Homo sapiens ENSG00000204228   hydroxysteroid (17-beta) dehydrogenase 8
Homo sapiens ENSG00000145439   carbonyl reductase 4
Leishmania braziliensis LbrM.27.2650   3-oxoacyl-ACP reductase, putative
Leishmania donovani LdBPK_272390.1   3-oxoacyl-ACP reductase, putative
Leishmania infantum LinJ.27.2390   3-oxoacyl-ACP reductase, putative
Leishmania major LmjF.27.2440   3-oxoacyl-ACP reductase, putative
Leishmania mexicana LmxM.27.2440   3-oxoacyl-(acyl-carrier protein) reductase-like protein
Loa Loa (eye worm) LOAG_13838   oxidoreductase
Loa Loa (eye worm) LOAG_07785   hypothetical protein
Loa Loa (eye worm) LOAG_02444   hypothetical protein
Mycobacterium leprae ML1807c   3-OXOACYL-[ACYL-CARRIER PROTEIN] REDUCTASE FABG1 (3-KETOACYL-ACYL CARRIER PROTEIN REDUCTASE) (MYCOLIC ACID BIOSYNTHESIS A PROTEI
Mus musculus ENSMUSG00000031641   carbonyl reductase 4
Mus musculus ENSMUSG00000073422   H2-K region expressed gene 6
Mycobacterium tuberculosis Rv1483   3-oxoacyl-[acyl-carrier protein] reductase FabG1 (3-ketoacyl-acyl carrier protein reductase) (mycolic acid biosynthesis a protei
Mycobacterium tuberculosis Rv1350   Probable 3-oxoacyl-[acyl-carrier protein] reductase FabG2 (3-ketoacyl-acyl carrier protein reductase)
Mycobacterium ulcerans MUL_3108   short-chain type dehydrogenase/reductase
Mycobacterium ulcerans MUL_0315   3-oxoacyl-ACP reductase
Mycobacterium ulcerans MUL_4844   short-chain type dehydrogenase/reductase
Mycobacterium ulcerans MUL_1052   short chain dehydrogenase
Mycobacterium ulcerans MUL_4361   short-chain type dehydrogenase/reductase
Mycobacterium ulcerans MUL_3168   short chain dehydrogenase
Mycobacterium ulcerans MUL_4354   short chain dehydrogenase
Mycobacterium ulcerans MUL_0327   oxidoreductase
Mycobacterium ulcerans MUL_4820   short-chain type dehydrogenase/reductase
Mycobacterium ulcerans MUL_1491   3-oxoacyl-ACP reductase
Mycobacterium ulcerans MUL_3898   3-ketoacyl-ACP reductase
Neospora caninum NCLIV_062520   3-ketoacyl-(Acyl-carrier-protein) reductase (EC 1.1.1.100), related
Oryza sativa 4351870   Os12g0242700
Oryza sativa 4326949   Os01g0930900
Oryza sativa 4351040   Os11g0654400
Oryza sativa 4329424   Os02g0503500
Oryza sativa 4351037   Os11g0652900
Oryza sativa 4335609   Os04g0376300
Onchocerca volvulus OVOC912  
Plasmodium berghei PBANKA_0823800   3-oxoacyl-[acyl-carrier-protein] reductase, putative
Plasmodium falciparum PF3D7_0922900   3-oxoacyl-[acyl-carrier-protein] reductase
Plasmodium knowlesi PKNH_0720900   3-oxoacyl-[acyl-carrier-protein] reductase, putative
Plasmodium vivax PVX_099555   3-oxoacyl-[acyl-carrier-protein] reductase, putative
Plasmodium yoelii PY02416   3-oxoacyl-acyl-carrier protein reductase precursor
Schistosoma japonicum Sjp_0210540   ko:K00065 2-deoxy-D-gluconate 3-dehydrogenase [EC1.1.1.125], putative
Schistosoma mansoni Smp_042680   3-oxoacyl-[ACP] reductase
Schmidtea mediterranea mk4.059771.00   Peroxisomal 2,4-dienoyl-CoA reductase
Schmidtea mediterranea mk4.038323.00   Peroxisomal 2,4-dienoyl-CoA reductase
Schmidtea mediterranea mk4.003605.01  
Schmidtea mediterranea mk4.003605.05  
Schmidtea mediterranea mk4.003605.02   Putative tropinone reductase
Schmidtea mediterranea mk4.007200.00  
Schmidtea mediterranea mk4.008358.00  
Schmidtea mediterranea mk4.004487.01  
Trypanosoma brucei gambiense Tbg972.10.14370   NAD or NADP dependent oxidoreductase,putative
Trypanosoma brucei gambiense Tbg.972.2.3240   3-oxoacyl-(acyl-carrier protein) reductase, putative
Trypanosoma brucei Tb927.2.5210   beta-ketoacyl-ACP reductase
Trypanosoma brucei Tb927.10.11930   beta-D-hydroxybutyrate dehydrogenase
Trypanosoma congolense TcIL3000_10_10090   short chain dehydrogenase, putative
Trypanosoma congolense TcIL3000_2_1320   beta-ketoacyl-ACP reductase
Trypanosoma cruzi TcCLB.507801.90   beta-ketoacyl-ACP reductase
Trypanosoma cruzi TcCLB.506567.70   NAD(P)-dependent oxidoreductase, putative
Trypanosoma cruzi TcCLB.507049.60   NAD(P)-dependent oxidoreductase, putative
Trypanosoma cruzi TcCLB.511627.150   beta-ketoacyl-ACP reductase
Toxoplasma gondii TGME49_217740   3-ketoacyl-(acyl-carrier-protein) reductase
Wolbachia endosymbiont of Brugia malayi Wbm0310   Short-chain alcohol dehydrogenase family enzyme

Essentiality

PF3D7_0922900 has one or more orthologs with essentiality data
Gene/Ortholog Organism Phenotype Source Study
mtu1373 Mycobacterium tuberculosis essential nmpdr
Tb927.2.5210 Trypanosoma brucei significant gain of fitness in bloodstream forms (3 days) alsford
Tb927.2.5210 Trypanosoma brucei no significant loss or gain of fitness in bloodstream forms (6 days) alsford
Tb927.2.5210 Trypanosoma brucei significant gain of fitness in procyclic forms alsford
Tb927.2.5210 Trypanosoma brucei no significant loss or gain of fitness in differentiation of procyclic to bloodstream forms alsford
Tb927.10.11930 Trypanosoma brucei significant gain of fitness in bloodstream forms (3 days) alsford
Tb927.10.11930 Trypanosoma brucei significant loss of fitness in bloodstream forms (6 days) alsford
Tb927.10.11930 Trypanosoma brucei no significant loss or gain of fitness in procyclic forms alsford
Tb927.10.11930 Trypanosoma brucei significant loss of fitness in differentiation of procyclic to bloodstream forms alsford
b1093 Escherichia coli essential goodall
b2842 Escherichia coli non-essential goodall
PBANKA_0823800 Plasmodium berghei Dispensable plasmo
TGME49_217740 Toxoplasma gondii Essentiality uncertain sidik
Show/Hide essentiality data references
  • blattner Systematic mutagenesis of the E. coli (MG1655) genome J Bacteriol 2004, 186:4921-4930
  • alsford High-throughput phenotyping using parallel sequencing of RNA interference targets in the African trypanosome Genome Res 2011, 21:915-924
  • 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.
  • 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.
  • keio Systematic single-gene knock-out mutants of E. coli K12 The Keio Collection
  • 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.
  • shigen Profiling of E. coli Chromosome (PEC) National Institute of Genetics, Japan
  • neb C. elegans RNAi phenotypes Data obtained from Wormbase WS150, curated by K. Chaudary and T. Carlow, New England Biolabs
  • gerdes Experimental determination and system-level analysis of essential genes in E. coli MG1655 Gerdes et al., J Bacteriol. 2003 185:5673-84
  • yeastgenome Systematic deletion of yeast genes Saccharomyces Genome Database

Phenotypes and Validation (curated)

Annotated phenotypes:

Affected Entity Phenotypic quality Occurs in Occurs at Evidence Observed in Drugs/Inhibitors
growth (GO:0040007) lethal (sensu genetics) (PATO:0000718) multi-cellular organism (CARO:0000012) bloodstream stage (PLO:0040) in vivo inhibition (TDR:00016) Plasmodium falciparum 8305  
Annotator: saralph@unimelb.edu.au. Comment: 012/Mar/09. References: 12646215 16225460

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

No validation data for this target

Associated compounds / Druggability

Druggability index (range: 0 to 1): 0.6

Known modulators for this target

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

Predicted associations

By orthology with druggable targets
Non orthologous druggable targets
By sequence similarity to non orthologous druggable targets
Species Target Length Identity Alignment span Linked Drugs Reference
Macaca mulatta Hydroxysteroid 11-beta dehydrogenase 1 140 aa 30.1% 146 aa Compounds References
Leishmania major pteridine reductase 1 288 aa 25.3% 281 aa Compounds References
Trypanosoma brucei pteridine reductase 1 268 aa 28.5% 267 aa Compounds References
Cochliobolus lunatus 17-beta-hydroxysteroid-dehydrogenase 270 aa 29.9% 268 aa Compounds References
Obtained from network model

Ranking Plot

Putative Drugs List

Compound Raw Global Species
0.0243 0.9572 0.5
0.0076 0.3786 1
0.0256 0.3131 0.5
0.0256 0.3131 0.5
0.0184 0.9309 1
0.0223 0.7904 1
0.021 0.8716 0.5
0.013 0.8847 1
0.0133 0.8786 1
0.0026 0.3431 1

Assayability

Assay information

  • Assay for L-Xylulose Reductase (1.1.1.10 ) Sigma-Aldrich
  • Automatic link to known assays based on EC numbers.
  • Inhibition of FabG ChEMBL
  • Inhibition of FabG
  • Inhibition of FabG at 100 uM ChEMBL
  • Inhibition of FabG at 100 uM
  • Inhibition of FabG in presence of acetoacetyl-CoA ChEMBL
  • Inhibition of FabG in presence of acetoacetyl-CoA
  • Inhibition of FabG in presence of NADPH ChEMBL
  • Inhibition of FabG in presence of NADPH
  • ChEMBL
  • Inhibition of Plasmodium falciparum FabG assessed as beta-hydroxyl C8-acyl carrier protein level by MALDI-TOF mass spectrometry
  • ChEMBL
  • Inhibition of Plasmodium falciparum recombinant FabG at 20 uM by spectrophotometric analysis
  • ChEMBL
  • Inhibition of Plasmodium falciparum FabG by spectrophotometric analysis
  • ChEMBL
  • Competitive inhibition of Plasmodium falciparum FabG using acetoacetyl-CoA as substrate by Michaelis-Menten steady state analysis
  • ChEMBL
  • Non-competitive inhibition of Plasmodium falciparum FabG using NADH as cofactor by Michaelis-Menten steady state analysis
  • ChEMBL
  • Inhibition of recombinant Plasmodium falciparum 3D7 FabG using acetoacetyl-CoA as substrate after 10 mins in presence of NADPH
  • BRENDA Assay
  • An enzyme with this EC number or name or sequence has been assayed in Plasmodium falciparum ( 4 )

Reagent availability

  • Reagent:
  • Target Type Source Notes
    PF3D7_0922900 purified protein BRENDA A protein with this EC number or name or sequence has been purified from Plasmodium falciparum ( 3 )

Bibliographic References

2 literature references were collected for this gene.

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Gene identifier PF3D7_0922900 (Plasmodium falciparum), 3-oxoacyl-[acyl-carrier-protein] reductase
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