Detailed view for PF3D7_1323000

Basic information

TDR Targets ID: 2113
Plasmodium falciparum, beta-hydroxyacyl-ACP dehydratase
Source Database / ID:  PlasmoDB   |   GeneDB   |   MPMP

pI: 10.1434 | Length (AA): 230 | MW (Da): 26211 | Paralog Number: 0

Signal peptide: Y | GPI Anchor: N | Predicted trans-membrane segments: 1

Druggability Group : DG1

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

PF07977   FabA-like domain

Gene Ontology

Mouse over links to read term descriptions.
GO:0020011   apicoplast  
GO:0008659   (3R)-hydroxymyristoyl-[acyl-carrier-protein] dehydratase activity  
GO:0005737   cytoplasm  
GO:0016836   hydro-lyase activity  
GO:0006633   fatty acid biosynthetic process  

Structural information

Modbase 3D models:

There are 3 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
82 230 2cf2 (C) 1002 1166 21.00 0 1 0.69 0.37
84 229 1z6b (A) 84 229 99.00 0 1 1.84 -1.96
84 229 1z6b (A) 84 229 99.99 0 1 1.84168 -1.36

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
  • 1Z6B:
  • Resolution Method # Atoms # Residues Dep. Date Pub. Date Mod. Date
PDB tag
  • 1ZHG:
  • Resolution Method # Atoms # Residues Dep. Date Pub. Date Mod. Date
PDB tag
  • 2OKH:
  • Resolution Method # Atoms # Residues Dep. Date Pub. Date Mod. Date
PDB tag
  • 2OKI:
  • Resolution Method # Atoms # Residues Dep. Date Pub. Date Mod. Date
PDB tag
  • 3AZ8:
  • Resolution Method # Atoms # Residues Dep. Date Pub. Date Mod. Date
PDB tag
  • 3AZ9:
  • Resolution Method # Atoms # Residues Dep. Date Pub. Date Mod. Date
PDB tag
  • 3AZA:
  • Resolution Method # Atoms # Residues Dep. Date Pub. Date Mod. Date
PDB tag
  • 3AZB:
  • Resolution Method # Atoms # Residues Dep. Date Pub. Date Mod. Date

Expression

Upregulation Percent Ranking Stage Dataset
Upper 60-80% percentile gametocyte, merozoite, sporozoite, early ring, early trophozoite, late ring, Oocyst, Ring. PlasmoDB Zanghi G
Upregulation Percent Ranking Stage Dataset
Mid 40-60% percentile intra-erythrocytic - 16 hs, intra-erythrocytic - 24 hs, intra-erythrocytic - 32 hs, early schizont, late schizont, late trophozoite. Otto TD PlasmoDB
Upregulation Percent Ranking Stage Dataset
Lower 20-40% percentile intra-erythrocytic - 0 hs, intra-erythrocytic - 8 hs, intra-erythrocytic - 40 hs, intra-erythrocytic - 48 hs, Sporozoite, Female Gametocyte. Otto TD Zanghi G Lasonder E
Upregulation Percent Ranking Stage Dataset
Lower 0-20% percentile Male Gametocyte. Lasonder E
Show/Hide expression data references
  • Otto TD New insights into the blood-stage transcriptome of Plasmodium falciparum using RNA-Seq.
  • Zanghi G A Specific PfEMP1 Is Expressed in P. falciparum Sporozoites and Plays a Role in Hepatocyte Infection.
  • Lasonder E Integrated transcriptomic and proteomic analyses of P. falciparum gametocytes. Molecular insight into sex-specific processes and translational repression.
  • PlasmoDB Data on upregulation of P. falciparum genes in different life cycle stages, combined from several microarray experiments available in PlasmoDB

Orthologs

Ortholog group members (OG5_130367)

Species Accession Gene Product
Arabidopsis thaliana AT5G10160   putative 3-hydroxyacyl-[acyl-carrier-protein] dehydratase
Arabidopsis thaliana AT2G22230   putative 3-hydroxyacyl-ACP dehydratase
Chlamydia trachomatis CT_532   3-hydroxyacyl-ACP dehydratase
Escherichia coli b0180   (3R)-hydroxymyristol acyl carrier protein dehydratase
Neospora caninum NCLIV_004340   hypothetical protein
Oryza sativa 4338898   Os05g0435700
Plasmodium berghei PBANKA_1338200   beta-hydroxyacyl-ACP dehydratase, putative
Plasmodium falciparum PF3D7_1323000   beta-hydroxyacyl-ACP dehydratase
Plasmodium knowlesi PKNH_1205800   beta-hydroxyacyl-ACP dehydratase, putative
Plasmodium vivax PVX_116720   beta-hydroxyacyl-ACP dehydratase precursor, putative
Plasmodium yoelii PY01586   beta-hydroxyacyl-ACP dehydratase precursor
Toxoplasma gondii TGME49_321570   beta-hydroxyacyl-acyl carrier protein dehydratase (FABZ)
Wolbachia endosymbiont of Brugia malayi Wbm0052   (3R)-hydroxymyristoyl-ACP dehydratase

Essentiality

PF3D7_1323000 has one or more orthologs with essentiality data
Gene/Ortholog Organism Phenotype Source Study
b0180 Escherichia coli essential goodall
PBANKA_1338200 Plasmodium berghei Dispensable plasmo
TGME49_321570 Toxoplasma gondii Probably non-essential sidik
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
  • yeastgenome Systematic deletion of yeast genes Saccharomyces Genome Database
  • blattner Systematic mutagenesis of the E. coli (MG1655) genome J Bacteriol 2004, 186:4921-4930
  • nmpdr Genome-scale essentiality datasets from published studies (M. tuberculosis) National Microbial Pathogen Data Resource
  • shigen Profiling of E. coli Chromosome (PEC) National Institute of Genetics, Japan
  • 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.
  • alsford High-throughput phenotyping using parallel sequencing of RNA interference targets in the African trypanosome Genome Res 2011, 21:915-924
  • keio Systematic single-gene knock-out mutants of E. coli K12 The Keio Collection
  • wormbase C. elegans RNAi experiments WormBase web site, http://www.wormbase.org, release WS170
  • neb C. elegans RNAi phenotypes Data obtained from Wormbase WS150, curated by K. Chaudary and T. Carlow, New England Biolabs

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 No drug identifiers listed for this gene.
Annotator: saralph@unimelb.edu.au. Comment: Drug: NAS-91, NAS-21. . References: 12930838 14684903 16643907 9770490

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

Known modulators for this target

Compound Source Reference
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
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
No additional associated druggable targets
Obtained from network model

Ranking Plot

Putative Drugs List

Compound Raw Global Species
0.0301972 0.497597 1
0.0316 0.3192 1
0.0233 0.2536 0.5
0.0256 0.3289 0.5
0.0226 0.3164 0.5774
0.0218 0.3289 0.5
0.0251 0.3206 0.5
0.0258 0.3213 1
0.0272 0.5 0.5
0.0227 0.3165 0.5774
0.0221 0.8423 0.5
0.0219 0.3175 0.5774
0.0253 0.2566 1
0.0291 0.7378 1
0.0223 0.3164 0.5782
0.0258 0.4083 0.5327
0.0236 0.316 0.5745
0.0258 0.4083 0.5327
0.0511 1 1
0.0491 0.5 0.5
0.0222 1 1
0.0251 1 0.5
0.0481 1 1
0.0223 0.7146 1
0.0232 0.3164 0.5745
0.0233 0.2606 1
0.0272 0.2701 1
0.0223 1 0.5
0.0444 0.3429 1
0.0232 0.3164 0.5745
0.0235 1 0.5
0.0235 0.3163 0.5745
0.0221 0.3168 0.5745
0.0251 1 0.5
0.0239 0.3462 1
0.0228 0.5089 1
0.0263 0.2972 0.4693
0.0233 0.5725 1
0.0231 0.7996 0.5
0.0272 0.2701 1
0.0258 0.4083 0.5327
0.0357722 0.935268 0.5
0.027 0.2535 0.5
0.0228 1 1
0.0219 0.3445 1
0.0235 0.3163 0.5745
0.0219 0.3528 0.5327
0.0258 0.4083 0.5327
0.0320232 0.262988 0.79537
0.025 0.2535 0.5
0.0272 0.3201 1
0.0221 0.2919 1
0.0228 0.3164 0.5745
0.0221 0.3168 0.5745
0.0221 0.3042 1
0.0226 0.3164 0.5745
0.0237 0.2507 0.5
0.0226 0.3261 0.5
0.0222 0.2521 1
0.0228 0.5089 1
0.0491 0.5 0.5
0.0233 0.5725 1
0.0237 0.2507 0.5
0.0223 0.2939 1
0.0219 0.3164 0.5745
0.0086 0.411 0.56
0.0272 0.6333 1
0.0272 0.262 1
0.0272 0.3289 0.5
0.0229 0.3732 0.5327
0.017395 0.32322 1
0.0222 0.2521 1
0.0228 0.2702 1
0.0362368 0.516233 0.791028
0.0272 0.3201 1
0.0229 0.2531 1
0.0241 0.286 1
0.0272 0.3201 1
0.0221 0.8423 0.5
0.0221 0.2787 1
0.0305577 0.262421 0.579494

Assayability

Assay information

  • Inhibition of FabZ ChEMBL
  • Inhibition of FabZ
  • Inhibition of FabZ at 100 uM ChEMBL
  • Inhibition of FabZ at 100 uM
  • ChEMBL
  • Inhibition of Plasmodium falciparum FabZ assessed as trans-2-octenoyl-acyl carrier protein level by MALDI-TOF mass spectrometry
  • ChEMBL
  • Inhibition of Plasmodium falciparum recombinant FabZ at 20 uM by spectrophotometric analysis
  • ChEMBL
  • Inhibition of Plasmodium falciparum FabZ by spectrophotometric analysis
  • ChEMBL
  • Competitive inhibition of Plasmodium falciparum FabZ using crotonyl-CoA as substrate by Michaelis-Menten steady state analysis
  • ChEMBL
  • Inhibition of recombinant Plasmodium falciparum FabZ using crotonoyl-CoA as substrate after 10 mins

Reagent availability

No reagent availability information for this target.

Bibliographic References

10 literature references were collected for this gene.

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

User comments

No user comments are available for this gene. Log in to add comments, or register.

Enter your comment

User ()
Gene identifier PF3D7_1323000 (Plasmodium falciparum), beta-hydroxyacyl-ACP dehydratase
Title for this comment
Comment