Detailed view for Rv0467

Basic information

TDR Targets ID: 6243
Mycobacterium tuberculosis, Isocitrate lyase Icl (isocitrase) (isocitratase)
Source Database / ID:  Tuberculist 

pI: 4.7918 | Length (AA): 428 | MW (Da): 47087 | Paralog Number: 2

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

Druggability Group : DG2

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

PF00463   Isocitrate lyase family

Gene Ontology

Mouse over links to read term descriptions.
GO:0004451   isocitrate lyase activity  
GO:0003824   catalytic activity  
GO:0008152   metabolic process  
GO:0019752   carboxylic acid metabolic process  

Structural information

Modbase 3D models:

There are 2 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
1 427 5dql (A) 1 427 99.99 0 1 2.18026 -0.91
4 409 3i4e (A) 1 410 67.00 0 1 1.7801 -0.71

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
  • 1F61:
  • Resolution Method # Atoms # Residues Dep. Date Pub. Date Mod. Date
PDB tag
  • 1F8I:
  • Resolution Method # Atoms # Residues Dep. Date Pub. Date Mod. Date
PDB tag
  • 1F8M:
  • Resolution Method # Atoms # Residues Dep. Date Pub. Date Mod. Date
PDB tag
  • 5DQL:
  • Resolution Method # Atoms # Residues Dep. Date Pub. Date Mod. Date
PDB tag
  • 6C4A:
  • Resolution Method # Atoms # Residues Dep. Date Pub. Date Mod. Date
PDB tag
  • 6C4C:
  • Resolution Method # Atoms # Residues Dep. Date Pub. Date Mod. Date

Expression

Upregulation Percent Ranking Stage Dataset
Upper 80-100% percentile Dormant phase, Dormant phase. hasan murphy
Show/Hide expression data references
  • murphy Identification of gene targets against dormant phase Mycobacterium tuberculosis infections.
  • hasan Prioritizing genomic drug targets in pathogens: application to Mycobacterium tuberculosis.

Orthologs

Ortholog group members (OG5_129572)

Species Accession Gene Product
Arabidopsis thaliana AT3G21720   isocitrate lyase
Candida albicans CaO19.14134   isocitrate lyase capable of functionally substituting for S. cerevisiae ICL1 (YER065C)
Candida albicans CaO19.6844   isocitrate lyase capable of functionally substituting for S. cerevisiae ICL1 (YER065C)
Dictyostelium discoideum DDB_G0273017   isocitrate lyase
Escherichia coli b4015   isocitrate lyase
Mycobacterium leprae ML1985c   PROBABLE ISOCITRATE LYASE AceA (ISOCITRASE) (ISOCITRATASE) (ICL)
Mycobacterium tuberculosis Rv0467   Isocitrate lyase Icl (isocitrase) (isocitratase)
Mycobacterium tuberculosis Rv1915   Probable isocitrate lyase AceAa [first part] (isocitrase) (isocitratase) (Icl)
Mycobacterium tuberculosis Rv1916   Probable isocitrate lyase AceAb [second part] (isocitrase) (isocitratase) (Icl)
Mycobacterium ulcerans MUL_4536   isocitrate lyase Icl
Mycobacterium ulcerans MUL_2943   isocitrate lyase AceAb
Oryza sativa 4343441   Os07g0529000
Saccharomyces cerevisiae YPR006C   methylisocitrate lyase ICL2
Saccharomyces cerevisiae YER065C   isocitrate lyase 1

Essentiality

Rv0467 has one or more orthologs with essentiality data
Gene/Ortholog Organism Phenotype Source Study
mtu1946 Mycobacterium tuberculosis non-essential nmpdr
b4015 Escherichia coli non-essential goodall
Show/Hide essentiality data references
  • yeastgenome Systematic deletion of yeast genes Saccharomyces Genome Database
  • 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
  • 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
  • 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
  • gerdes Experimental determination and system-level analysis of essential genes in E. coli MG1655 Gerdes et al., J Bacteriol. 2003 185:5673-84
  • 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

Phenotypes and Validation (curated)

Annotated phenotypes:

Affected Entity Phenotypic quality Occurs in Occurs at Evidence Observed in Drugs/Inhibitors
catalytic activity (GO:0003824) decreased (PATO:0000468) in vitro (MI:0492) inferred from specific protein inhibition (ECO:0000020) Mycobacterium tuberculosis 142023   259505   311792   565944   565945   566321   568416   589985  
Annotator: crowther@u.washington.edu. Comment: 2007-12-12. References: 10572116
growth (GO:0040007) decreased (PATO:0000468) inferred from animal model system (ECO:0000179) Mycobacterium tuberculosis No drug identifiers listed for this gene.
Annotator: crowther@u.washington.edu. Comment: 2007-12-12. References: 10963599
growth (GO:0040007) decreased (PATO:0000468) inferred from in vitro culture assay (ECO:0000182) Mycobacterium tuberculosis 565944   565945  
Annotator: crowther@u.washington.edu. Comment: 2007-12-12. References: 10963599 15895072 16201909
growth (GO:0040007) lethal (sensu genetics) (PATO:0000718) inferred from animal model system (ECO:0000179) Mycobacterium tuberculosis No drug identifiers listed for this gene.
Annotator: crowther@u.washington.edu. Comment: 2007-12-12. References: 15895072
response to drug (GO:0042493) decreased sensitivity toward (PATO:0001550) inferred from over expression (ECO:0000120) Mycobacterium tuberculosis 565944   565945  
Annotator: crowther@u.washington.edu. Comment: 2007-12-12. References: 15895072

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): 0.2

Known modulators for this target

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

Predicted associations

By orthology with druggable targets
Species Known druggable target Linked compounds Reference
Mycobacterium tuberculosis Probable isocitrate lyase AceAa [first part] (isocitrase) (isocitratase) (Icl) Compounds References
Mycobacterium tuberculosis Probable isocitrate lyase AceAb [second part] (isocitrase) (isocitratase) (Icl) Compounds References
Candida albicans isocitrate lyase capable of functionally substituting for S. cerevisiae ICL1 (YER065C) Compounds References
Magnaporthe oryzae (strain 70-15 / FGSC 8958) (Rice blast fungus)(Pyricularia oryzae) Isocitrate lyase 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
0.0454 0.812 0.5
0.0246 0.3406 1
0.3918 1 1
0.1019 1 0.5
0.3025 1 1
0.3213 1 1
0.2106 1 1
0.1033 1 0.5
0.1702 0.3091 1
0.0627 0.5961 1
0.2027 1 1
0.1801 1 0.5
0.2027 1 1
0.0696 0.2803 1
0.1016 0.2985 0.2974
0.0462 0.4934 0.4934
0.0311 0.4891 1
0.0887 0.6595 0.831
0.2683 0.369 0.3688
0.0504 1 1
0.0381 0.5731 1
0.1577 1 1
0.0696 0.2803 1
0.0682 0.4388 1
0.1577 1 1
0.0627 0.3723 0.8333
0.3213 1 1
0.0559 1 0.5
0.1898 1 0.5
0.1735 0.7153 0.9152
0.0447 0.3561 0.6788
0.0823 0.2709 0.2637
0.0507 1 1
0.1569 0.6478 0
0.0875 0.4457 1
0.1681 1 1
0.0702 1 1
0.1715 0.4184 0.6847
0.0487 0.2511 0.2465
0.3289 0.265 0.347
0.1162 1 0.5
0.0541 1 1
0.1577 1 1
0.118 1 0.5
0.063 0.3929 1
0.0627 0.7019 1
0.0627 1 1
0.0502 0.7146 1
0.0525 0.3252 0.5
0.0346 0.3922 1
0.0542 1 1
0.0572 0.4425 1
0.0462 0.281 1
0.251 0.7754 1
0.0293 0.4109 1
0.0571 0.3436 0.3545
0.0526 1 1
0.0507 1 1
0.1031 1 0.5
0.1016 0.2985 0.2974
0.0788 0.7694 1
0.0526 1 1
0.1168 0.7139 0.7383
0.0987 0.5552 0.5505
0.0506 0.3596 0.4507
0.0627 1 0.5
0.3893 0.3472 0.3472
0.0493 0.2749 1
0.0875 0.4457 1
0.0511 1 1
0.1169 1 1
0.2493 1 1
0.0981 1 1
0.3137 1 1
0.0498 1 1
0.0502 1 0.5
0.0303 0.3104 0.3964
0.0627 0.8223 0.5
0.1801 1 0.5
0.0981 0.6043 0.6029
0.0515 0.2749 1
0.1485 1 1
0.22159 0.677339 0.677339
0.1735 0.7153 0.9152
0.1881 1 1
0.2027 1 1
0.1195 1 1
0.2683 0.369 0.3688
0.251 0.7754 1
0.2683 0.369 0.3688
0.0526 1 1
0.1121 0.7653 0.5
0.117 1 1
0.2683 0.369 0.3688
0.1626 1 0.5
0.0583 0.4921 1
0.1694 1 1
0.0574 0.75 1
0.0311 0.4891 1
0.3893 0.3472 0.3472
0.1019 1 0.5
0.1058 1 0.5
0.0616 0.6064 0.7288
0.0532 1 0.5
0.0559 0.5044 1
0.1207 1 1
0.0583 0.4921 1
0.3137 1 1
0.0559 1 1
0.0627 0.3847 1
0.3814 0.2595 0.3768
0.0559002 1 0.5
0.4383 1 1
0.0483 0.7036 0.5
0.0819 0.3605 1
0.042 0.6561 0.6561
0.2008 1 1
0.0627 1 1
0.121 1 1
0.0696 0.2803 1
0.1477 1 1
0.1506 0.6478 0
0.0502 0.7146 1
0.048 0.6829 1
0.0627 1 0.5
0.0546 0.5008 0.5
0.162 1 1
0.169 0.378 0.9005
0.0938 0.6249 0.6217
0.0914 0.628 1
0.0195 0.4446 1
0.0462 0.2842 1
0.0875 0.4457 1
0.1008 0.2554 0.2534
0.3025 1 1
0.1882 0.6721 0
0.0507 1 1
0.0914 0.628 1
0.1169 1 1
0.0627 0.3847 1
0.1195 1 1
0.0525 0.3252 0.5
0.1077 0.4388 1
0.1734 0.9107 0.9107
0.4444 1 1
0.0543 1 0.5
0.0275 0.289 1
0.0539 1 0.5
0.3817 1 1
0.0537 0.349 1
0.0506 0.3596 0.4507
0.0507 1 1
0.6358 0.2636 0.2636
0.052 0.6898 1
0.0476 0.2734 0.5963
0.2683 0.369 0.3688
0.169 0.378 0.9005
0.0512 1 0.5
0.0555 0.2843 1
0.0627 0.3217 0.3203
0.1648 0.2588 1
0.169 0.378 0.9005
0.1882 0.5654 1
0.187 0.3182 0.3164
0.1121 0.7653 0.5
0.1015 0.4652 0.4619
0.0506 0.4847 1
0.0987 0.5552 0.5505
0.1169 1 0.5
0.0987 0.5552 0.5505
0.0861 0.6249 0.6217
0.1019 1 0.5
0.1725 0.6797 0.6797
0.0574 0.3393 1
0.0392 1 1
0.1735 0.7153 0.9152
0.4913 0.6303 1
0.1567 0.3191 0.6822
0.0558 0.7288 0.5
0.0507 1 1
0.1577 1 1
0.1949 1 1
0.0546 0.5008 0.5
0.1577 1 1
0.0554 1 1
0.0447 0.2705 0.3121
0.2401 1 1
0.1882 0.5654 1
0.1477 1 1
0.1162 1 0.5
0.0524 0.2843 1
0.0447 0.2705 0.3121
0.1731 1 1
0.1801 1 0.5
0.0246 0.3406 1
0.187 0.3182 0.3164
0.1731 1 1
0.1577 1 1
0.0559 1 0.5
0.0875 0.4457 1
0.0327 0.2751 1
0.1157 1 0.5
0.6738 0.3381 1
0.0943 0.2984 0.2918
0.0506 1 0.5
0.0594 0.596 1
0.1791 0.2838 0.2821
0.0509 1 0.5
0.2027 1 1
0.0627 0.5961 1
0.169 0.378 0.9005
0.251 0.7754 1
0.0267 0.4481 0.9385
0.6625 0.901 1
0.1949 1 1
0.1882 1 1
0.0696 0.2803 1
0.1153 1 0.5
0.1696 1 1
0.2955 1 1
0.0368 0.5594 0.5
0.0293 0.4109 1
0.042 0.6561 0.6561
0.3231 1 1
0.0914 0.628 1
0.0546 1 1
0.1145 0.5 0.5
0.0627 1 0.5
0.3213 0.3471 0.3464
0.0507 0.8023 0.6821
0.0549 1 0.5
0.21 0.971 1
0.1801 1 0.5
0.0515 0.2749 1
0.041 1 0.5
0.0549 1 1
0.0275 0.289 1

Assayability

Assay information

  • Assay for Isocitrate Lyase (4.1.3.1 ) Sigma-Aldrich
  • Automatic link to known assays based on EC numbers.
  • ChEMBL
  • Inhibition of Mycobacterium tuberculosis recombinant isocitrate lyase expressed in Escherichia coli BL21 (DE3) using isocitrate as substrate after 10 mins by spectrometric analysis
  • ChEMBL
  • Inhibition of Mycobacterium tuberculosis recombinant isocitrate lyase expressed in Escherichia coli BL21 (DE3) using isocitrate as substrate at 1 mg/mL by spectrometric analysis relative to control
  • ChEMBL
  • Percent inhibition of Mycobacterium tuberculosis isocitrate lyase (ICL) at 10 uM
  • ChEMBL
  • Percent inhibition of Mycobacterium tuberculosis isocitrate lyase (ICL) at 100 uM
  • ChEMBL
  • Inhibition of Mycobacterium tuberculosis isocitrate lyase at 10 mM
  • ChEMBL
  • Inhibition of Mycobacterium tuberculosis isocitrate lyase at 100 mM
  • ChEMBL
  • Inhibition of Mycobacterium tuberculosis isocitrate lyase
  • ChEMBL
  • Inhibition of Mycobacterium tuberculosis H37Rv isocitrate lyase expressed in Escherichia coli BL21(DE3) using (+)-potassium Ds-threo-isocitrate as substrate assessed as glyoxylate phenyl hydrazone formation at 100 umol/L by spectrophotometry
  • ChEMBL
  • Inhibition of Mycobacterium tuberculosis H37Rv isocitrate lyase expressed in Escherichia coli HB101 at 10 umol/L

Reagent availability

No reagent availability information for this target.

Bibliographic References

24 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

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Gene identifier Rv0467 (Mycobacterium tuberculosis), Isocitrate lyase Icl (isocitrase) (isocitratase)
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