Detailed view for Rv1077

Basic information

TDR Targets ID: 5730
Mycobacterium tuberculosis, Probable cystathionine beta-synthase Cbs (serine sulfhydrase) (beta-thionase) (hemoprotein H-450)
Source Database / ID:  Tuberculist 

pI: 4.9418 | Length (AA): 464 | MW (Da): 48635 | 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

PF00291   Pyridoxal-phosphate dependent enzyme
PF00571   CBS domain

Gene Ontology

Mouse over links to read term descriptions.
GO:0005737   cytoplasm  
GO:0004122   cystathionine beta-synthase activity  
GO:0003824   catalytic activity  
GO:0030170   pyridoxal phosphate binding  
GO:0019343   cysteine biosynthetic process via cystathionine  
GO:0008152   metabolic process  

Structural information

Modbase 3D models:

There are 5 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
1 298 4i1y (A) 1 296 50.00 0 1 1.06614 0.03
1 302 2q3b (A) 1 300 47.00 0 1 1.24776 -0.7
2 463 3pc3 (A) 44 510 30.00 0 1 1.30199 0.26
2 462 4coo (A) 75 548 37.00 0 1 1.41433 0
5 305 1o58 (A) 0 291 43.00 0 1 1.20501 -0.9

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
Mid 40-60% 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_126662)

Species Accession Gene Product
Arabidopsis thaliana AT3G59760   cysteine synthase C
Arabidopsis thaliana AT4G14880   O-acetylserine (thiol) lyase (OAS-TL) isoform A1
Arabidopsis thaliana AT2G43750   O-acetylserine (thiol) lyase (OAS-TL) isoform oasB
Arabidopsis thaliana AT3G22460   O-acetylserine (thiol) lyase (OAS-TL) isoform A2
Arabidopsis thaliana AT3G04940   cysteine synthase D1
Arabidopsis thaliana AT5G28030   bifunctional cystathionine gamma-lyase/cysteine synthase
Arabidopsis thaliana AT5G28020   cysteine synthase D2
Brugia malayi Bm1_32965   cbs-prov protein
Brugia malayi Bm1_32960   Pyridoxal-phosphate dependent enzyme family protein
Candida albicans CaO19.12011   cystathionine beta-synthase
Candida albicans CaO19.4536   cystathionine beta-synthase
Caenorhabditis elegans CELE_C17G1.7   Protein CYSL-1
Caenorhabditis elegans CELE_F54A3.4   Protein CBS-2
Caenorhabditis elegans CELE_ZC373.1   Protein CBS-1, isoform B
Caenorhabditis elegans CELE_R08E5.2   Protein CYSL-3, isoform B
Caenorhabditis elegans CELE_K10H10.2   Protein CYSL-2
Dictyostelium discoideum DDB_G0267386   cystathionine beta-synthase
Drosophila melanogaster Dmel_CG1753   Cystathionine beta-synthase
Escherichia coli b2414   cysteine synthase A, O-acetylserine sulfhydrolase A subunit
Escherichia coli b2421   cysteine synthase B (O-acetylserine sulfhydrolase B)
Entamoeba histolytica EHI_160930   cysteine synthase A, putative
Entamoeba histolytica EHI_060340   cysteine synthase A, putative
Entamoeba histolytica EHI_024230   cysteine synthase A, putative
Homo sapiens ENSG00000160200   cystathionine-beta-synthase
Homo sapiens ENSG00000274276   cystathionine beta-synthase-like
Leishmania braziliensis LbrM.17.0230   cystathionine beta-synthase
Leishmania braziliensis LbrM.35.3820   cysteine synthase
Leishmania donovani LdBPK_170300.1   cystathionine beta-synthase
Leishmania donovani LdBPK_363750.1   cysteine synthase
Leishmania infantum LinJ.36.3750   cysteine synthase
Leishmania infantum LinJ.17.0300   cystathionine beta-synthase
Leishmania major LmjF.17.0250   cystathionine beta-synthase
Leishmania major LmjF.36.3590   cysteine synthase
Leishmania mexicana LmxM.17.0250   cystathionine beta-synthase
Leishmania mexicana LmxM.36.3590   cysteine synthase, putative
Loa Loa (eye worm) LOAG_04327   cbs-prov protein
Mycobacterium leprae ML2396c   Probable cystathionine beta-synthase CBS (Serine sulfhydrase) (Beta-thionase) (Hemoprotein H-450)
Mycobacterium leprae ML0839c   PROBABLE CYSTEINE SYNTHASE A CYSK (O-ACETYLSERINE SULFHYDRYLASE A) (O-ACETYLSERINE (THIOL)-LYASE A) (CSASE A)
Mus musculus ENSMUSG00000024039   cystathionine beta-synthase
Mycobacterium tuberculosis Rv1077   Probable cystathionine beta-synthase Cbs (serine sulfhydrase) (beta-thionase) (hemoprotein H-450)
Mycobacterium tuberculosis Rv2334   Cysteine synthase a CysK1 (O-acetylserine sulfhydrylase A) (O-acetylserine (thiol)-lyase A) (CSASE A)
Mycobacterium tuberculosis Rv1336   Cysteine synthase B CysM (CSASE B) (O-phosphoserine sulfhydrylase B) (O-phosphoserine (thiol)-lyase B)
Mycobacterium ulcerans MUL_0203   cystathionine beta-synthase
Mycobacterium ulcerans MUL_1465   cysteine synthase a CysK1
Mycobacterium ulcerans MUL_0242   cysteine synthase B
Neospora caninum NCLIV_027350   Protein ZC373.1, partially confirmed by transcript evidence, related
Oryza sativa 4340142   Os06g0149900
Oryza sativa 4340140   Os06g0149700
Oryza sativa 4341321   Os06g0564500
Oryza sativa 9266140   Os02g0222100
Oryza sativa 4341322   Os06g0564700
Oryza sativa 4334101   Os03g0747800
Oryza sativa 4327819   Os01g0978100
Oryza sativa 4352839   Os12g0625000
Oryza sativa 9268401   Os05g0591500
Saccharomyces cerevisiae YGR155W   cystathionine beta-synthase CYS4
Schistosoma japonicum Sjp_0008740   expressed protein
Schistosoma mansoni Smp_125070.1   cysteine synthase
Schistosoma mansoni Smp_125070.2   cysteine synthase
Schmidtea mediterranea mk4.008627.03   Cystathionine beta-synthase
Schmidtea mediterranea mk4.007603.03   Cystathionine beta-synthase
Schmidtea mediterranea mk4.042742.02  
Schmidtea mediterranea mk4.072323.00   Cystathionine beta-synthase
Schmidtea mediterranea mk4.037021.00  
Schmidtea mediterranea mk4.005683.00  
Trypanosoma brucei gambiense Tbg972.11.8590   cystathionine beta-synthase, putative
Trypanosoma brucei Tb11.02.5400   cystathionine beta-synthase, putative
Trypanosoma cruzi TcCLB.508177.120   serine sulfhydrylase
Trypanosoma cruzi TcCLB.510381.10   cystathionine beta-synthase, putative
Trypanosoma cruzi TcCLB.508241.140   cystathionine beta-synthase, putative
Trypanosoma cruzi TcCLB.511691.10   cystathionine beta-synthase
Trypanosoma cruzi TcCLB.507165.50   cysteine synthase, putative
Trypanosoma cruzi TcCLB.506905.50   serine sulfhydrylase
Trypanosoma cruzi TcCLB.508175.360   serine sulfhydrylase
Trypanosoma cruzi TcCLB.511691.20   cystathionine beta-synthase
Trypanosoma cruzi TcCLB.507793.20   cysteine synthase, putative
Trypanosoma cruzi TcCLB.508177.129   cystathionine beta-synthase, putative
Trypanosoma cruzi TcCLB.509149.9   cystathionine beta-synthase
Trypanosoma cruzi TcCLB.508177.110   serine sulfhydrylase
Toxoplasma gondii TGME49_259180   CBS family protein
Toxoplasma gondii TGME49_325200   pyridoxal-phosphate dependent superfamily protein
Trichomonas vaginalis TVAG_387920   cysteine synthase, putative
Trichomonas vaginalis TVAG_430060   cysteine synthase, putative
Trichomonas vaginalis TVAG_547520   threonine synthase, putative
Trichomonas vaginalis TVAG_337280   cysteine synthase, putative
Trichomonas vaginalis TVAG_040090   cysteine synthase, putative
Trichomonas vaginalis TVAG_368890   cysteine synthase, putative
Trichomonas vaginalis TVAG_337290   cysteine synthase, putative
Trichomonas vaginalis TVAG_391870   threonine synthase, putative

Essentiality

Rv1077 has direct evidence of essentiality
Gene/Ortholog Organism Phenotype Source Study
mtu1094 this record Mycobacterium tuberculosis non-essential nmpdr
mtu2375 Mycobacterium tuberculosis non-essential nmpdr
mtu1359 Mycobacterium tuberculosis non-essential nmpdr
Tb11.02.5400 Trypanosoma brucei no significant loss or gain of fitness in bloodstream forms (3 days) alsford
Tb11.02.5400 Trypanosoma brucei no significant loss or gain of fitness in bloodstream forms (6 days) alsford
Tb11.02.5400 Trypanosoma brucei no significant loss or gain of fitness in procyclic forms alsford
Tb11.02.5400 Trypanosoma brucei significant gain of fitness in differentiation of procyclic to bloodstream forms alsford
b2414 Escherichia coli non-essential goodall
b2421 Escherichia coli non-essential goodall
YGR155W Saccharomyces cerevisiae inviable yeastgenome
TGME49_259180 Toxoplasma gondii Probably non-essential sidik
TGME49_325200 Toxoplasma gondii Probably non-essential sidik
Show/Hide essentiality data references
  • wormbase C. elegans RNAi experiments WormBase web site, http://www.wormbase.org, release WS170
  • blattner Systematic mutagenesis of the E. coli (MG1655) genome J Bacteriol 2004, 186:4921-4930
  • 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.
  • 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.
  • 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
  • gerdes Experimental determination and system-level analysis of essential genes in E. coli MG1655 Gerdes et al., J Bacteriol. 2003 185:5673-84
  • 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.
  • 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
  • shigen Profiling of E. coli Chromosome (PEC) National Institute of Genetics, Japan

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): 0.2

Known modulators for this target

No chemical compounds associated to this gene

Predicted associations

By orthology with druggable targets
Species Known druggable target Linked compounds Reference
Mycobacterium tuberculosis Cysteine synthase a CysK1 (O-acetylserine sulfhydrylase A) (O-acetylserine (thiol)-lyase A) (CSASE A) 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
0.0022 0.3773 0.5
0.0008 1 0.5
0.0139 1 1
0.0159 0.483 1
0.014 0.5 0.5
0.0148 0.5 0.5
0.0075 0.9022 1
0.014 0.5 0.5
0.0152 0.3993 1
0.0114 0.504 0.5
0.0073 0.8669 1
0.0141 0.3912 1
0.0166 0.4624 0.5
0.0164 0.5 0.5
0.0139 0.459 0.459
0.0127 0.3304 1
0.0012 1 0.5
0.0136 0.4136 0.4576
0.0128 0.5 0.5
0.014 1 1

Assayability

Assay information

No assay information for this target.

Reagent availability

No reagent availability information for this target.

Bibliographic References

1 literature reference was collected for this gene.

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Gene identifier Rv1077 (Mycobacterium tuberculosis), Probable cystathionine beta-synthase Cbs (serine sulfhydrase) (beta-thionase) (hemoprotein H-450)
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