Detailed view for Rv3858c

Basic information

TDR Targets ID: 6165
Mycobacterium tuberculosis, Probable NADH-dependent glutamate synthase (small subunit) GltD (L-glutamate synthase) (L-glutamate synthetase) (NADH-glutamate

Source Database / ID:  Tuberculist 

pI: 5.5406 | Length (AA): 488 | MW (Da): 53452 | Paralog Number: 1

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

PF07992   Pyridine nucleotide-disulphide oxidoreductase
PF14691   Dihydroprymidine dehydrogenase domain II, 4Fe-4S cluster

Gene Ontology

Mouse over links to read term descriptions.
GO:0016639   oxidoreductase activity, acting on the CH-NH2 group of donors, NAD or NADP as acceptor  
GO:0016491   oxidoreductase activity  
GO:0009055   electron carrier activity  
GO:0051536   iron-sulfur cluster binding  
GO:0008152   metabolic process  
GO:0006537   glutamate biosynthetic process  
GO:0055114   oxidation reduction  

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
12 474 4ylf (B) 3 463 18.00 0 1 1.13817 0.52
12 472 4ylf (B) 3 461 35.00 0 1 1.34757 -0.25
136 178 5mog (A) 101 138 39.00 0 0.8 0.486215 -0.88
145 184 1sez (A) 14 53 55.00 0 0.87 0.691067 -0.02

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
Lower 20-40% percentile Dormant phase. hasan
Upregulation Percent Ranking Stage Dataset
Lower 0-20% percentile Dormant phase. murphy
Show/Hide expression data references
  • hasan Prioritizing genomic drug targets in pathogens: application to Mycobacterium tuberculosis.
  • murphy Identification of gene targets against dormant phase Mycobacterium tuberculosis infections.

Orthologs

Ortholog group members (OG5_126892)

Species Accession Gene Product
Arabidopsis thaliana AT5G53460   glutamate synthase 1 [NADH]
Arabidopsis thaliana AT2G41220   ferredoxin-dependent glutamate synthase 2
Arabidopsis thaliana AT5G04140   ferredoxin-dependent glutamate synthase 1
Brugia malayi Bm1_40910   glutamate synthase
Candida albicans CaO19.13636   likely glutamate synthase similar to S. cerevisiae GLT1 (YDL171C)
Candida albicans CaO19.6257   likely glutamate synthase similar to S. cerevisiae GLT1 (YDL171C)
Caenorhabditis elegans CELE_W07E11.1   Protein W07E11.1, isoform B
Drosophila melanogaster Dmel_CG9674   CG9674 gene product from transcript CG9674-RD
Escherichia coli b2468   putative oxidoreductase, FeS binding subunit/NAD/FAD-binding subunit
Escherichia coli b3212   glutamate synthase, large subunit
Escherichia coli b2887   putative oxidoreductase, Fe-S subunit/nucleotide-binding subunit
Escherichia coli b3213   glutamate synthase, 4Fe-4S protein, small subunit
Echinococcus granulosus EgrG_000644000   glutamate synthase
Entamoeba histolytica EHI_110520   glutamate synthase beta subunit, putative
Entamoeba histolytica EHI_045340   glutamate synthase beta subunit, putative
Echinococcus multilocularis EmuJ_000644000   glutamate synthase
Giardia lamblia GL50803_7195   Glutamate synthase
Loa Loa (eye worm) LOAG_03492   hypothetical protein
Mycobacterium leprae ML0062   Probable NADH-dependent glutamate synthase (small subunit) GltD (L-glutamate synthase) (L-glutamate synthetase) (NADH-glutamate
Mycobacterium leprae ML0061   Probable ferredoxin-dependent glutamate synthase (large subunit) GltB (L-glutamate synthase) (L-glutamate synthetase) (NADH-glut
Mycobacterium tuberculosis Rv3859c   Probable ferredoxin-dependent glutamate synthase [NADPH] (large subunit) GltB (L-glutamate synthase) (L-glutamate synthetase) (N
Mycobacterium tuberculosis Rv3858c   Probable NADH-dependent glutamate synthase (small subunit) GltD (L-glutamate synthase) (L-glutamate synthetase) (NADH-glutamate
Mycobacterium ulcerans MUL_5036   glutamate synthase subunit beta
Mycobacterium ulcerans MUL_5037   ferredoxin-dependent glutamate synthase large subunit GltB
Oryza sativa 9268275   Os07g0676200
Oryza sativa 4339561   Os05g0555600
Oryza sativa 4344164   Os07g0658400
Oryza sativa 4324398   Os01g0681900
Onchocerca volvulus OVOC5367   Putative glutamate synthase
Plasmodium berghei PBANKA_1009500   NAD(P)H-dependent glutamate synthase, putative
Plasmodium falciparum PF3D7_1435300   NAD(P)H-dependent glutamate synthase, putative
Plasmodium knowlesi PKNH_0421900   NAD(P)H-dependent glutamate synthase, putative
Plasmodium vivax PVX_084770   NAD(P)H-dependent glutamate synthase, putative
Plasmodium yoelii PY03719   NAD(P)H-dependent glutamate synthase-related
Saccharomyces cerevisiae YDL171C   glutamate synthase (NADH)
Schistosoma japonicum Sjp_0087440   Putative glutamate synthase [NADPH], putative
Schistosoma japonicum Sjp_0067700   ko:K00264 glutamate synthase (NADPH) [EC1.4.1.13], putative
Schistosoma mansoni Smp_128380.2   glutamate synthase
Schistosoma mansoni Smp_128380.1   glutamate synthase
Schistosoma mansoni Smp_128380.3   glutamate synthase
Schmidtea mediterranea mk4.005136.00   Putative glutamate synthase
Schmidtea mediterranea mk4.009183.01  
Schmidtea mediterranea mk4.009183.00  
Schmidtea mediterranea mk4.000669.03   Putative glutamate synthase
Treponema pallidum TP0735   oxidoreductase

Essentiality

Rv3858c has direct evidence of essentiality
Gene/Ortholog Organism Phenotype Source Study
mtu3926 Mycobacterium tuberculosis essential nmpdr
mtu3925 this record Mycobacterium tuberculosis essential nmpdr
b2468 Escherichia coli non-essential goodall
b2887 Escherichia coli non-essential goodall
b3212 Escherichia coli non-essential goodall
b3213 Escherichia coli non-essential goodall
CELE_W07E11.1 Caenorhabditis elegans embryonic lethal wormbase
CELE_W07E11.1 Caenorhabditis elegans larval arrest wormbase
CELE_W07E11.1 Caenorhabditis elegans slow growth wormbase
PBANKA_1009500 Plasmodium berghei Slow plasmo
Show/Hide essentiality data references
  • wormbase C. elegans RNAi experiments WormBase web site, http://www.wormbase.org, release WS170
  • 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.
  • 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
  • neb C. elegans RNAi phenotypes Data obtained from Wormbase WS150, curated by K. Chaudary and T. Carlow, New England Biolabs
  • 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.
  • shigen Profiling of E. coli Chromosome (PEC) National Institute of Genetics, Japan
  • yeastgenome Systematic deletion of yeast genes Saccharomyces Genome Database
  • gerdes Experimental determination and system-level analysis of essential genes in E. coli MG1655 Gerdes et al., J Bacteriol. 2003 185:5673-84
  • keio Systematic single-gene knock-out mutants of E. coli K12 The Keio Collection
  • 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.

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

Known modulators for this target

No chemical compounds associated to this gene

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
Mycobacterium tuberculosis Probable thioredoxin reductase TrxB2 (TRXR) (TR) 335 aa 26.5% 351 aa Compounds References

Obtained from network model
No druggable targets predicted through repurposing network model

Assayability

Assay information

No assay information for this target.

Reagent availability

No reagent availability information for this target.

Bibliographic References

4 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 Rv3858c (Mycobacterium tuberculosis), Probable NADH-dependent glutamate synthase (small subunit) GltD (L-glutamate synthase) (L-glutamate synthetase) (NADH-glutamate
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