Detailed view for PF3D7_1440300

Basic information

TDR Targets ID: 2712
Plasmodium falciparum, porphobilinogen synthase
Source Database / ID:  PlasmoDB   |   GeneDB   |   MPMP

pI: 8.5219 | Length (AA): 451 | MW (Da): 53188 | 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

PF00490   Delta-aminolevulinic acid dehydratase

Gene Ontology

Mouse over links to read term descriptions.
GO:0020011   apicoplast  
GO:0046872   metal ion binding  
GO:0004655   porphobilinogen synthase activity  
GO:0003824   catalytic activity  
GO:0033014   tetrapyrrole biosynthetic process  
GO:0008152   metabolic process  

Structural information

Modbase 3D models:

There are 8 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
85 429 1h7n (A) 4 340 27.00 0 1 1.1 -1.44
95 429 1w5q (A) 10 335 35.00 0 1 1.28 -1.67
103 428 2c1h (A) 16 328 37.00 0 1 1.19 -1.79
85 429 1aw5 (A) 11 340 29.00 0 1 1.05637 -0.19
86 429 3obk (A) 9 343 39.00 0 1 1.29275 -0.85
95 429 2c15 (A) 10 335 33.00 0 1 1.21479 -0.87
86 430 3obk (A) 9 344 39.00 0 1 1.28207 -0.78
95 429 2c15 (A) 10 335 33.00 0 1 1.22789 -1.06

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:

No structure availble in the PDB for this protein

Expression

Upregulation Percent Ranking Stage Dataset
Upper 60-80% percentile Oocyst. Zanghi G
Upregulation Percent Ranking Stage Dataset
Mid 40-60% percentile merozoite, early trophozoite, late trophozoite. PlasmoDB
Upregulation Percent Ranking Stage Dataset
Lower 20-40% percentile intra-erythrocytic - 16 hs, intra-erythrocytic - 24 hs, intra-erythrocytic - 32 hs, intra-erythrocytic - 40 hs, intra-erythrocytic - 48 hs, Ring, Sporozoite, Male Gametocyte. Otto TD Zanghi G Lasonder E
Upregulation Percent Ranking Stage Dataset
Lower 0-20% percentile intra-erythrocytic - 0 hs, intra-erythrocytic - 8 hs, Female Gametocyte. Otto TD Lasonder E
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
  • Lasonder E Integrated transcriptomic and proteomic analyses of P. falciparum gametocytes. Molecular insight into sex-specific processes and translational repression.
  • Otto TD New insights into the blood-stage transcriptome of Plasmodium falciparum using RNA-Seq.

Orthologs

Ortholog group members (OG5_127486)

Species Accession Gene Product
Arabidopsis thaliana AT1G69740   putative delta-aminolevulinic acid dehydratase
Babesia bovis BBOV_II001120   delta-aminolevulinic acid dehydratase, putative
Candida albicans CaO19.8517   porphobilinogen synthase
Candida albicans CaO19.898   porphobilinogen synthase
Chlamydia trachomatis CT_633   delta-aminolevulinic acid dehydratase
Dictyostelium discoideum DDB_G0269444   delta-aminolevulinate dehydratase
Drosophila melanogaster Dmel_CG10335   Porphobilinogen synthase
Escherichia coli b0369   5-aminolevulinate dehydratase (porphobilinogen synthase)
Echinococcus granulosus EgrG_000471300   delta aminolevulinic acid dehydratase
Echinococcus multilocularis EmuJ_000471300   delta aminolevulinic acid dehydratase
Homo sapiens ENSG00000148218   aminolevulinate dehydratase
Mycobacterium leprae ML2419c   PROBABLE DELTA-AMINOLEVULINIC ACID DEHYDRATASE HEMB (PORPHOBILINOGEN SYNTHASE) (ALAD) (ALADH)
Mus musculus ENSMUSG00000028393   aminolevulinate, delta-, dehydratase
Mycobacterium tuberculosis Rv0512   Probable delta-aminolevulinic acid dehydratase HemB (porphobilinogen synthase) (ALAD) (ALADH)
Mycobacterium ulcerans MUL_4601   delta-aminolevulinic acid dehydratase
Neospora caninum NCLIV_008230   Delta-aminolevulinic acid dehydratase (EC 4.2.1.24), related
Oryza sativa 4341997   Os06g0704600
Plasmodium berghei PBANKA_1304100   porphobilinogen synthase, putative
Plasmodium falciparum PF3D7_1440300   porphobilinogen synthase
Plasmodium knowlesi PKNH_1242100   porphobilinogen synthase, putative
Plasmodium vivax PVX_118480   delta-aminolevulinic acid dehydratase, putative
Plasmodium yoelii PY04302   porphobilinogen synthase, putative
Saccharomyces cerevisiae YGL040C   porphobilinogen synthase HEM2
Schistosoma japonicum Sjp_0075570   ko:K01698 porphobilinogen synthase [EC4.2.1.24], putative
Schistosoma mansoni Smp_045810.1   porphobilinogen synthase
Schistosoma mansoni Smp_045810.2   porphobilinogen synthase
Schmidtea mediterranea mk4.029516.02  
Schmidtea mediterranea mk4.000123.05   Delta-aminolevulinic acid dehydratase
Toxoplasma gondii TGME49_253900   parasite porphobilinogen synthase PBGS
Wolbachia endosymbiont of Brugia malayi Wbm0373   delta-aminolevulinic acid dehydratase

Essentiality

PF3D7_1440300 has one or more orthologs with essentiality data
Gene/Ortholog Organism Phenotype Source Study
b0369 Escherichia coli essential goodall
YGL040C Saccharomyces cerevisiae inviable yeastgenome
PBANKA_1304100 Plasmodium berghei Essential plasmo
TGME49_253900 Toxoplasma gondii Probably 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
  • alsford High-throughput phenotyping using parallel sequencing of RNA interference targets in the African trypanosome Genome Res 2011, 21:915-924
  • neb C. elegans RNAi phenotypes Data obtained from Wormbase WS150, curated by K. Chaudary and T. Carlow, New England Biolabs
  • nmpdr Genome-scale essentiality datasets from published studies (M. tuberculosis) National Microbial Pathogen Data Resource
  • yeastgenome Systematic deletion of yeast genes Saccharomyces Genome Database
  • wormbase C. elegans RNAi experiments WormBase web site, http://www.wormbase.org, release WS170
  • 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.
  • 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.
  • blattner Systematic mutagenesis of the E. coli (MG1655) genome J Bacteriol 2004, 186:4921-4930
  • shigen Profiling of E. coli Chromosome (PEC) National Institute of Genetics, Japan
  • 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) lethal (sensu genetics) (PATO:0000718) multi-cellular organism (CARO:0000012) bloodstream stage (PLO:0040) in vivo inhibition (TDR:00016) Plasmodium falciparum 416673  
Annotator: saralph@unimelb.edu.au. Comment: 012/Mar/09. References: 9501849
catalytic activity (GO:0003824) decreased (PATO:0000468) in vitro (MI:0492) inferred from specific protein inhibition (ECO:0000020) Plasmodium falciparum 416673  
Annotator: saralph@unimelb.edu.au. Comment: 012/Mar/09. References: 9501849

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
Curated by TDRTargets References

Predicted associations

By orthology with druggable targets
Species Known druggable target Linked compounds Reference
Wolbachia sp. subsp. Brugia malayi (strain TRS) Delta-aminolevulinic acid dehydratase Compounds References
Pisum sativum Delta-aminolevulinic acid dehydratase, chloroplastic Compounds References
Pseudomonas aeruginosa (strain ATCC 15692 / PAO1 / 1C / PRS 101 / LMG12228) Delta-aminolevulinic acid dehydratase Compounds References
Escherichia coli 5-aminolevulinate dehydratase (porphobilinogen synthase) Compounds References
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
0.0671 0.3909 1
0.0517 1 0.5
0.0671 0.3909 1
0.0987 0.6805 1
0.0209 0.3728 1
0.0999 1 0.5
0.0207 0.4079 1
0.0227 0.7175 1
0.0445 0.5306 1
0.0414 1 0.5
0.0987 0.6805 1
0.0844 0.2876 1
0.0211 0.2859 0.5036
0.0258 0.8395 1
0.0517 1 0.5
0.0956 1 0.5
0.0217 0.3364 0.5806
0.0451 1 0.5
0.0445 0.5306 1
0.0226 0.7619 1
0.0483 1 0.5
0.0237 0.7827 1
0.0671 0.3909 1
0.0483 1 0.5
0.0209 0.3728 1
0.0445 0.5306 1
0.0227 0.7826 1
0.0517 0.3113 0.5
0.0445 0.5306 1
0.0483 1 0.5
0.0479 1 1
0.0209 0.362 1
0.0445 0.5306 1
0.0462 0.5254 0.5

Assayability

Assay information

  • Assay for γ-Aminolevulinate Dehydratase (4.2.1.24 ) Sigma-Aldrich
  • Automatic link to known assays based on EC numbers.
  • BRENDA Assay
  • An enzyme with this EC number or name or sequence has been assayed in Plasmodium falciparum ( 1 )

Reagent availability

  • Pfal007037AAB;
  • Type Source Notes
    soluble recombinant protein Structural Genomics for Pathogenic Protozoa (SGPP) Pfal007037; Recombinant protein: truncated; Source: P falciparum; delta-aminolevulinic acid dehydratase EC 4.2.1.24 ;
  • Reagent:
  • Target Type Source Notes
    PF3D7_1440300 cloned gene BRENDA A gene with this EC number or name or sequence has been cloned from Plasmodium falciparum ( 1 )

Bibliographic References

11 literature references were collected for this gene.

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Gene identifier PF3D7_1440300 (Plasmodium falciparum), porphobilinogen synthase
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