Detailed view for PF3D7_0618500

Basic information

TDR Targets ID: 4536
Plasmodium falciparum, malate dehydrogenase
Source Database / ID:  PlasmoDB   |   GeneDB   |   MPMP

pI: 7.3443 | Length (AA): 313 | MW (Da): 34041 | Paralog Number: 1

Signal peptide: N | 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

PF00056   lactate/malate dehydrogenase, NAD binding domain
PF02866   lactate/malate dehydrogenase, alpha/beta C-terminal domain

Gene Ontology

Mouse over links to read term descriptions.
GO:0016616   oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor  
GO:0005739   mitochondrion  
GO:0016615   malate dehydrogenase activity  
GO:0016491   oxidoreductase activity  
GO:0005488   binding  
GO:0003824   catalytic activity  
GO:0044262   cellular carbohydrate metabolic process  
GO:0019752   carboxylic acid metabolic process  
GO:0008152   metabolic process  
GO:0006099   tricarboxylic acid cycle  
GO:0006096   glycolysis  
GO:0005975   carbohydrate metabolic process  
GO:0055114   oxidation reduction  

Structural information

Modbase 3D models:

There are 7 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
2 307 2hjr (A) 15 322 43.00 0 1 1.6 -2.15
2 313 1pzg (A) 21 332 40.00 0 1 1.53 -1.84
2 311 1sov (A) 21 331 42.00 0 1 1.67 -2.03
2 306 2hjr (A) 15 321 43.00 0 1 1.62044 -1.42
2 313 1pzg (A) 21 332 38.00 0 1 1.52981 -1.09
2 312 4plg (A) 9 325 49.00 0 1 1.67461 -1.37
2 311 4plv (A) 5 321 50.00 0 1 1.66742 -1.33

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
  • 5NFR:
  • Resolution Method # Atoms # Residues Dep. Date Pub. Date Mod. Date

Expression

Upregulation Percent Ranking Stage Dataset
Upper 80-100% percentile intra-erythrocytic - 48 hs, Oocyst, Female Gametocyte, Male Gametocyte. Otto TD Zanghi G Lasonder E
Upregulation Percent Ranking Stage Dataset
Upper 60-80% percentile intra-erythrocytic - 32 hs, intra-erythrocytic - 40 hs, sporozoite. Otto TD PlasmoDB
Upregulation Percent Ranking Stage Dataset
Mid 40-60% percentile intra-erythrocytic - 0 hs, intra-erythrocytic - 16 hs, intra-erythrocytic - 24 hs, Ring, Sporozoite. Otto TD Zanghi G
Upregulation Percent Ranking Stage Dataset
Lower 20-40% percentile intra-erythrocytic - 8 hs. Otto TD
Show/Hide expression data references
  • 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.
  • 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

Orthologs

Ortholog group members (OG5_126911)

Species Accession Gene Product
Arabidopsis thaliana AT4G17260   lactate/malate dehydrogenase family protein
Babesia bovis BBOV_IV011270   lactate dehydrogenase
Brugia malayi Bm1_43730   lactate dehydrogenase.
Caenorhabditis elegans CELE_F13D12.2   Protein LDH-1
Cryptosporidium hominis Chro.70062   malate dehydrogenase
Cryptosporidium hominis Chro.70063   lactate dehydrogenase
Cryptosporidium parvum cgd7_480   lactate dehydrogenase, adjacent gene encodes predicted malate dehydrogenase
Cryptosporidium parvum cgd7_470   malate dehydrogenase, adjacent gene encodes predicted lactate dehydrogenase
Drosophila melanogaster Dmel_CG13334   CG13334 gene product from transcript CG13334-RB
Drosophila melanogaster Dmel_CG10160   Ecdysone-inducible gene L3
Echinococcus granulosus EgrG_000467700   L lactate dehydrogenase
Echinococcus granulosus EgrG_000661000   lactate dehydrogenase protein
Echinococcus granulosus EgrG_000608500   lactate dehydrogenase a
Echinococcus granulosus EgrG_000634800   L lactate dehydrogenase B chain
Echinococcus granulosus EgrG_000660800   lactate dehydrogenase a
Entamoeba histolytica EHI_067860   malate dehydrogenase, putative
Echinococcus multilocularis EmuJ_000608500   lactate dehydrogenase a
Echinococcus multilocularis EmuJ_000634800   L lactate dehydrogenase B chain
Echinococcus multilocularis EmuJ_000660800   lactate dehydrogenase a
Echinococcus multilocularis EmuJ_000661000   lactate dehydrogenase a
Echinococcus multilocularis EmuJ_000007100   lactate dehydrogenase protein
Echinococcus multilocularis EmuJ_000467700   L lactate dehydrogenase
Homo sapiens ENSG00000111716   lactate dehydrogenase B
Homo sapiens ENSG00000166800   lactate dehydrogenase A-like 6A
Homo sapiens ENSG00000134333   lactate dehydrogenase A
Homo sapiens ENSG00000166796   lactate dehydrogenase C
Leishmania braziliensis LbrM.20.0020   malate dehydrogenase, putative
Leishmania donovani LdBPK_340160.1   malate dehydrogenase, putative
Leishmania infantum LinJ.34.0160   malate dehydrogenase, putative
Leishmania major LmjF.34.0150   malate dehydrogenase, putative
Leishmania mexicana LmxM.33.0150   malate dehydrogenase, putative
Loa Loa (eye worm) LOAG_12271   hypothetical protein
Mus musculus ENSMUSG00000030246   lactate dehydrogenase B
Mus musculus ENSMUSG00000030851   lactate dehydrogenase C
Mus musculus ENSMUSG00000063229   lactate dehydrogenase A
Neospora caninum NCLIV_011120   Malate dehydrogenase (EC 1.1.1.37), related
Neospora caninum NCLIV_042910   Malate dehydrogenase (EC 1.1.1.37), related
Neospora caninum NCLIV_032330   Malate dehydrogenase (NAD) (EC 1.1.1.37) (Precursor), related
Oryza sativa 4339856   Os06g0104900
Oryza sativa 4328012   Os02g0105400
Plasmodium berghei PBANKA_1117700   malate dehydrogenase, putative
Plasmodium berghei PBANKA_1340100   L-lactate dehydrogenase
Plasmodium falciparum PF3D7_1324900   L-lactate dehydrogenase
Plasmodium falciparum PF3D7_0618500   malate dehydrogenase
Plasmodium knowlesi PKNH_1131900   malate dehydrogenase, putative
Plasmodium knowlesi PKNH_1203900   L-lactate dehydrogenase
Plasmodium vivax PVX_114050   malate dehydrogenase, putative
Plasmodium vivax PVX_116630   lactate dehydrogenase
Plasmodium yoelii PY03376   malate dehydrogenase
Plasmodium yoelii PY03885   l-lactate dehydrogenase
Schistosoma japonicum Sjp_0117410   L-lactate dehydrogenase B chain, putative
Schistosoma japonicum Sjp_0054460   ko:K00016 L-lactate dehydrogenase [EC1.1.1.27], putative
Schistosoma japonicum Sjp_0054470   L-lactate dehydrogenase A chain, putative
Schistosoma japonicum Sjp_0110090   ko:K00016 L-lactate dehydrogenase [EC1.1.1.27], putative
Schistosoma mansoni Smp_038960   L-lactate dehydrogenase
Schistosoma mansoni Smp_038950   malate dehydrogenase
Schmidtea mediterranea mk4.012266.00   L-lactate dehydrogenase
Schmidtea mediterranea mk4.001801.04   L-lactate dehydrogenase
Schmidtea mediterranea mk4.053509.00   L-lactate dehydrogenase
Schmidtea mediterranea mk4.027145.02   L-lactate dehydrogenase
Schmidtea mediterranea mk4.005513.02   L-lactate dehydrogenase
Schmidtea mediterranea mk4.001167.10   L-lactate dehydrogenase
Toxoplasma gondii TGME49_291040   lactate dehydrogenase LDH2
Toxoplasma gondii TGME49_318430   malate dehydrogenase MDH
Toxoplasma gondii TGME49_232350   lactate dehydrogenase LDH1
Theileria parva TP01_1182   L-lactate dehydrogenase, putative
Wolbachia endosymbiont of Brugia malayi Wbm0244   malate dehydrogenase

Essentiality

PF3D7_0618500 has one or more orthologs with essentiality data
Gene/Ortholog Organism Phenotype Source Study
PBANKA_1117700 Plasmodium berghei Slow plasmo
PBANKA_1340100 Plasmodium berghei Essential plasmo
TGME49_232350 Toxoplasma gondii Probably non-essential sidik
TGME49_318430 Toxoplasma gondii Probably non-essential sidik
TGME49_291040 Toxoplasma gondii Probably non-essential sidik
Show/Hide essentiality data references
  • nmpdr Genome-scale essentiality datasets from published studies (M. tuberculosis) National Microbial Pathogen Data Resource
  • alsford High-throughput phenotyping using parallel sequencing of RNA interference targets in the African trypanosome Genome Res 2011, 21:915-924
  • 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
  • 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.
  • 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.
  • 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
  • wormbase C. elegans RNAi experiments WormBase web site, http://www.wormbase.org, release WS170
  • shigen Profiling of E. coli Chromosome (PEC) National Institute of Genetics, Japan
  • yeastgenome Systematic deletion of yeast genes Saccharomyces Genome Database

Phenotypes and Validation (curated)

We have no manually annotated phenotypes for this target. What does this mean? / Care to help?

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): 0.8

Known modulators for this target

Compound Source Reference
ChEMBL23 References
ChEMBL23 References
ChEMBL23 References

Predicted associations

By orthology with druggable targets
Species Known druggable target Linked compounds Reference
Homo sapiens lactate dehydrogenase C Compounds References
Plasmodium falciparum L-lactate dehydrogenase Compounds References
Homo sapiens lactate dehydrogenase B 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
0.0485 1 1
0.0919 1 1
0.0189 0.3717 0.5
0.045 0.4448 1
0.0093 1 1
0.0717 0.8148 1
0.0111 1 1
0.0087 1 1
0.161358 1 1
0.0319 0.5451 1
0.0883 0.2722 1
0.0843 1 1
0.0265 0.6234 1
0.0839 1 1
0.0527 0.5275 1
0.0099 1 1
0.0631 1 1
0.0353 1 1
0.0425 0.2736 1
0.0154 1 1
0.0644 1 1
0.0145 1 1
0.114 0.6612 1
0.0879 0.2756 1
0.0099 1 1
0.0526 1 1
0.0089 0.2759 1
0.0155 0.305 1
0.009 1 1
0.0833 0.6076 1
0.0868 1 1
0.0413 1 1
0.0616 1 1
0.0154 1 1
0.0111 1 1
0.029 1 1
0.0596 1 1
0.0584 1 1
0.0738 1 1
0.107 1 1
0.0707 1 1
0.0473 0.3312 1
0.0135 1 1
0.0183 0.5948 0.6079
0.0597 0.6445 1
0.0099 1 1
0.0411 1 1
0.0111 1 1
0.0056 1 1
0.017 0.4383 1
0.0111 1 1
0.0185 0.2871 1
0.0104 0.3056 1
0.0601 0.5179 0.9712
0.0794 1 1
0.0099 1 1
0.009 1 1
0.0197 1 1
0.0777 1 0.5
0.0111 1 1
0.0281 1 1
0.0783 1 1
0.0154 1 1
0.0298 0.2816 1
0.04 0.4764 0.9027
0.0639 0.5 0.5
0.0105429 1 1
0.0934 1 1
0.0635 1 1
0.0192 0.4457 1
0.1467 1 1
0.0255 1 1
0.00523329 1 0.5
0.0111 1 1
0.0585 0.653 1
0.0742 1 1
0.0341 1 1
0.0631 1 1
0.0154 0.429 0.9116
0.0153 1 1
0.0154 1 1
0.0624 0.4508 1
0.1689 1 1
0.054 0.6655 1
0.1065 1 1
0.0152 1 1
0.1033 1 1
0.0559 0.6159 1
0.0639 0.4797 1
0.0489 1 1
0.157803 1 1
0.0646 0.7726 1
0.0612 0.6616 1
0.0099 1 1
0.2209 1 1
0.0111 1 1
0.0919 1 1
0.0798 1 1
0.0729 1 1
0.0767 1 0.5
0.0638 1 1
0.0111 0.2545 0
0.0448 0.7102 1
0.157803 1 1
0.0099 1 1
0.0152 0.3576 1
0.0544 1 1
0.0418 0.3666 1
0.0557 1 1
0.0453 0.7124 1
0.0514 1 1
0.0216 0.2501 0.9954
0.0099 1 1
0.0099 1 1
0.0573 0.5919 0.9432
0.114 0.6612 1
0.0832 0.3897 1
0.1412 1 1
0.1516 1 1
0.0056 1 1
0.1682 1 1
0.0137 0.3251 1
0.0137 0.9354 1
0.0056 1 1
0.0595 1 1
0.0097 0.3315 1
0.0539 0.6641 1
0.0188 0.8143 0.5
0.04 0.4764 0.9027
0.0111 1 1
0.0099 1 1
0.1114 1 1
0.0056 0.7494 0.5
0.00522164 1 0.5
0.0616 1 1
0.0639 0.5 0.5
0.0134 1 1
0.1939 1 1
0.055 0.646 1
0.0791 1 1
0.0634 0.3624 1
0.0405 1 1
0.0529 1 1
0.0177 0.4156 0.5
0.0879 0.2756 1
0.0056 0.4605 0.5
0.0126 0.5984 1
0.0364 1 1
0.0135 0.6383 1
0.032 0.2952 1
0.04 0.4764 0.9027
0.00640072 0.46482 0.519188
0.0271 1 1
0.098 1 1
0.1448 1 1
0.0596 1 1
0.0574 1 1
0.0111 1 1
0.0141 0.4647 0.5
0.269 1 1
0.0449 0.7241 1
0.0453 0.7124 1
0.0573 0.5919 0.9432
0.0618 1 1
0.0093 1 0.5
0.0095 0.2733 1
0.0632 1 1
0.0154 1 1
0.009 1 1
0.0889 1 1
0.0111 1 1
0.0403 0.7904 1
0.0091 1 1
0.0046 0.9126 1
0.0099 1 1
0.0874 1 1
0.0752 1 1
0.0134 0.4209 1
0.0789 1 1
0.0341 1 1
0.0053 0.6345 1
0.0293 0.3063 1
0.0081 0.4562 1
0.1163 1 1
0.0056 1 0.5
0.064 1 1
0.0089 1 1
0.0192 0.4457 1
0.0097 0.3315 1
0.147 1 1
0.0624 0.4508 1
0.0154 1 1
0.0099 1 1
0.0339 1 1
0.195 1 1
0.0453 0.7124 1
0.0099 1 1
0.0099 1 1
0.0494 0.4942 1
0.0573 0.5919 0.9432
0.009 1 1
0.0459 1 1
0.0839 1 1
0.016 1 0.5
0.0717 0.6889 1
0.0812 0.9737 1
0.0099 1 1
0.014 0.5495 1
0.0111 1 1
0.0099 1 1
0.0832 0.3897 1
0.0169 1 1
0.0056 1 1
0.0819 1 1
0.0154 1 1
0.04 0.4764 0.9027
0.0529 1 1
0.014 0.5495 1
0.1043 1 1
0.0322 1 1
0.0573 0.5919 0.9432
0.0712 0.5296 1
0.0099 1 1
0.1103 1 1
0.1333 1 1
0.0099 1 1
0.0098 0.3355 1
0.0601 1 1
0.0346 1 1
0.0463 1 1
0.0463 1 1
0.2312 1 1
0.0108965 1 0.5
0.0883 0.2722 1
0.073 1 1
0.0111 1 1
0.0056 1 1
0.063 0.4772 1
0.0099 1 1
0.0549 0.3471 1
0.0154 1 1
0.0266 0.3061 1
0.0247 1 1
0.0573 0.3424 0.5
0.0596 1 1
0.0833 0.6076 1
0.0504 1 1
0.0111 1 1
0.0099 1 1
0.0056 1 1
0.0506 0.8505 1
0.0056 1 1
0.0056 1 1
0.0053 1 0.5
0.0099 1 1
0.0736 1 1
0.0549 0.3471 1
0.0649 1 1
0.0111 1 1
0.0111 1 1
0.0833 0.6076 1
0.0346 1 1
0.0099 1 1
0.0833 0.6076 1
0.0183 1 1
0.1366 1 1
0.0281 1 1
0.1056 1 1
0.0833 0.6076 1
0.0552 1 1
0.0298 0.2816 1
0.0111 1 0.5
0.0056 1 1
0.0579 1 1
0.00536163 1 0.5
0.0629 0.5011 1
0.098 1 1
0.1477 1 1
0.0587 0.3508 1
0.054 0.6655 1
0.0449 0.7241 1
0.0339 1 1
0.063 0.4772 1
0.0095 1 1
0.1794 1 1
0.0833 0.6076 1
0.0186 1 1
0.0099 1 1
0.0778 1 1
0.0573 0.5919 0.9432
0.0099 1 1
0.0099 1 1
0.0111 1 1
0.0107169 1 0.5
0.1516 1 1
0.0099 1 1
0.0559 0.6159 1
0.0468 1 1
0.0266 0.3061 1
0.0111 1 1
0.0185 1 1
0.00518542 1 0.5
0.027 1 1
0.1103 1 1
0.0134 0.4209 1
0.053 1 1
0.0281 1 1
0.0103 1 1
0.0049 0.3011 1
0.0417 0.3312 1
0.0111 1 1
0.0266 0.3061 1
0.1326 1 1
0.0099 1 1
0.0639 0.4797 1
0.0053 1 0.5
0.1114 1 1
0.0183 0.5948 0.6079
0.0315 1 1
0.027 1 1
0.0628 0.3888 1
0.0361 1 1
0.0609 0.6484 1
0.0111 1 1
0.0266 0.3061 1
0.0453 0.7124 1
0.0111 1 1
0.0793 1 1
0.1794 1 1
0.044 0.3132 1
0.0745 1 1
0.0683 1 1

Assayability

Assay information

  • Assay for Malic Dehydrogenase (1.1.1.37 ) Sigma-Aldrich
  • Automatic link to known assays based on EC numbers.
  • Inhibition of Plasmodium falciparum MDH ChEMBL
  • Inhibition of Plasmodium falciparum MDH
  • BRENDA Assay
  • An enzyme with this EC number or name or sequence has been assayed in Plasmodium falciparum ( 1 )

Reagent availability

  • Reagent:
  • Target Type Source Notes
    PF3D7_0618500 cloned gene BRENDA A gene with this EC number or name or sequence has been cloned from Plasmodium falciparum ( 1 )

Bibliographic References

19 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.

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Gene identifier PF3D7_0618500 (Plasmodium falciparum), malate dehydrogenase
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