Detailed view for Rv2379c

Basic information

TDR Targets ID: 6415
Mycobacterium tuberculosis, Peptide synthetase MbtF (peptide synthase)

Source Database / ID:  Tuberculist 

pI: 5.6934 | Length (AA): 1461 | MW (Da): 156748 | 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

PF00501   AMP-binding enzyme
PF00550   Phosphopantetheine attachment site
PF00668   Condensation domain
PF13193   AMP-binding enzyme C-terminal domain

Gene Ontology

Mouse over links to read term descriptions.
GO:0031177   phosphopantetheine binding  
GO:0048037   cofactor binding  
GO:0016874   ligase activity  
GO:0003824   catalytic activity  
GO:0000036   acyl carrier activity  
GO:0008152   metabolic process  

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
11 1029 2vsq (A) 5 1037 29.00 0 1 1.00267 0.12
461 1460 5u89 (A) 447 1482 19.00 0.00064 1 0.837263 0.8
472 932 4d4i (A) 5 489 34.00 0 1 0.687737 -0.35
476 912 5wmm (A) 38 470 42.00 0 1 0.66631 0.4
477 1367 5u89 (A) 463 1383 34.00 0 1 0.854056 0.73
961 1031 5ejd (A) 3 75 23.00 0 1 0.455697 -1.43
1048 1381 2xhg (A) 17 371 24.00 0.00000000033 1 0.397811 0.38

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 Dormant phase. murphy
Upregulation Percent Ranking Stage Dataset
Lower 20-40% percentile Dormant phase. hasan
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_126718)

Species Accession Gene Product
Arabidopsis thaliana AT5G35930   AMP-dependent synthetase and ligase family protein
Brugia malayi Bm1_50860   AMP-binding enzyme family protein
Brugia malayi Bm1_08580   AMP-binding enzyme family protein
Brugia malayi Bm1_41065   oxidoreductase, short chain dehydrogenase/reductase family protein
Brugia malayi Bm1_21980   AMP-binding enzyme family protein
Candida albicans CaO19.10487   alpha-aminoadipate reductase large subunit
Candida albicans CaO19.2970   alpha-aminoadipate reductase large subunit
Caenorhabditis elegans CELE_W09D6.1   Protein W09D6.1, isoform B
Caenorhabditis elegans CELE_Y66D12A.14   Protein Y66D12A.14
Caenorhabditis elegans CELE_C41A3.1   Protein C41A3.1
Dictyostelium discoideum DDB_G0290145   hypothetical protein
Drosophila melanogaster Dmel_CG13401   CG13401 gene product from transcript CG13401-RA
Drosophila melanogaster Dmel_CG3331   ebony
Escherichia coli b0586   enterobactin synthase multienzyme complex component, ATP-dependent
Echinococcus granulosus EgrG_000451000   acyl coenzyme A synthetase family
Echinococcus multilocularis EmuJ_000451000   acyl coenzyme A synthetase family
Homo sapiens ENSG00000157426   aminoadipate-semialdehyde dehydrogenase
Leishmania braziliensis LbrM.28.2240   hypothetical protein, unknown function
Leishmania donovani LdBPK_282190.1   AMP-binding enzyme/Ankyrin repeats (3 copies), putative
Leishmania infantum LinJ.28.2190   hypothetical protein, unknown function
Leishmania major LmjF.28.2050   hypothetical protein, unknown function
Leishmania mexicana LmxM.28.2050   hypothetical protein, unknown function
Loa Loa (eye worm) LOAG_01735   AMP-binding enzyme family protein
Loa Loa (eye worm) LOAG_07277   AMP-binding enzyme family protein
Loa Loa (eye worm) LOAG_01652   hypothetical protein
Loa Loa (eye worm) LOAG_09506   hypothetical protein
Loa Loa (eye worm) LOAG_00871   oxidoreductase
Mycobacterium leprae ML1996   POSSIBLE PEPTIDE SYNTHETASE NRP (PEPTIDE SYNTHASE)
Mus musculus ENSMUSG00000055923   aminoadipate-semialdehyde dehydrogenase
Mycobacterium tuberculosis Rv2380c   Peptide synthetase MbtE (peptide synthase)
Mycobacterium tuberculosis Rv2379c   Peptide synthetase MbtF (peptide synthase)
Mycobacterium tuberculosis Rv0101   Probable peptide synthetase Nrp (peptide synthase)
Mycobacterium ulcerans MUL_3633   non-ribosomal peptide synthetase MbtF
Mycobacterium ulcerans MUL_2638   peptide synthetase Nrp (peptide synthase)
Mycobacterium ulcerans MUL_2753   oxidoreductase
Mycobacterium ulcerans MUL_3634   non-ribosomal peptide synthetase MbtE
Mycobacterium ulcerans MUL_4858   non-ribosomal peptide synthetase
Oryza sativa 4339893   Os06g0111600
Onchocerca volvulus OVOC7029  
Onchocerca volvulus OVOC7760  
Onchocerca volvulus OVOC7761  
Onchocerca volvulus OVOC9416  
Saccharomyces cerevisiae YBR115C   L-aminoadipate-semialdehyde dehydrogenase
Schistosoma japonicum Sjp_0083170   ko:K00142 aminoadipate-semialdehyde dehydrogenase [EC1.2.1.31], putative
Schistosoma mansoni Smp_171910   hypothetical protein
Schmidtea mediterranea mk4.031911.00  
Schmidtea mediterranea mk4.022197.01  
Schmidtea mediterranea mk4.031911.01  
Schmidtea mediterranea mk4.056960.00  
Schmidtea mediterranea mk4.002331.11  
Schmidtea mediterranea mk4.002331.12  
Schmidtea mediterranea mk4.022197.00  

Essentiality

Rv2379c has one or more orthologs with essentiality data
Gene/Ortholog Organism Phenotype Source Study
b0586 Escherichia coli non-essential goodall
Show/Hide essentiality data references
  • 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
  • alsford High-throughput phenotyping using parallel sequencing of RNA interference targets in the African trypanosome Genome Res 2011, 21:915-924
  • yeastgenome Systematic deletion of yeast genes Saccharomyces Genome Database
  • 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.
  • shigen Profiling of E. coli Chromosome (PEC) National Institute of Genetics, Japan
  • wormbase C. elegans RNAi experiments WormBase web site, http://www.wormbase.org, release WS170
  • 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
  • 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

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 Fatty-acid-AMP ligase FadD28 (fatty-acid-AMP synthetase) (fatty-acid-AMP synthase) 580 aa 22.8% 561 aa Compounds References
Photuris pennsylvanica Luciferin 4-monooxygenase 545 aa 21.2% 553 aa Compounds References
Yersinia pestis AMP-binding enzyme family protein 525 aa 26.1% 510 aa Compounds References
Mycobacterium tuberculosis Bifunctional enzyme MbtA: salicyl-AMP ligase (SAL-AMP ligase) + salicyl-S-ArCP synthetase 565 aa 26.2% 545 aa Compounds References

Obtained from network model

Ranking Plot


Putative Drugs List


Compound Raw Global Species
0.0088 0.2627 0.0546
0.0193 0.2636 0.2636
0.0193 0.2636 0.2636
0.0021 0.2636 0.2636

Assayability

Assay information

No assay information for this target.

Reagent availability

No reagent availability information for this target.

Bibliographic References

No literature references available for this target.

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Gene identifier Rv2379c (Mycobacterium tuberculosis), Peptide synthetase MbtF (peptide synthase)
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