Detailed view for Rv2215
Basic information
Mycobacterium tuberculosis, DlaT, dihydrolipoamide acyltransferase, E2 component of pyruvate dehydrogenase
Source Database / ID: Tuberculist
pI: 4.6408 |
Length (AA): 553 |
MW (Da): 57088 |
Paralog Number:
0
Signal peptide: N | GPI Anchor: | Predicted trans-membrane segments: 0
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
Network
Gene Ontology
GO:0008152 metabolic process
Metabolic Pathways
Structural information
Modbase 3D models:
There are 3 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 |
|---|---|---|---|---|---|---|---|---|---|
| 126 | 195 | 2l5t (A) | 6 | 75 | 53.00 | 0 | 0.72 | 0.696282 | 0.23 |
| 245 | 281 | 2eq9 (C) | 132 | 168 | 49.00 | 0 | 1 | 0.737208 | -1.15 |
| 296 | 544 | 4n72 (A) | 384 | 623 | 30.00 | 0 | 1 | 0.773571 | -0.04 |
Help me make sense of these data.
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:
Expression
Orthologs
Ortholog group members (OG5_127362)
| Species | Accession | Gene Product |
|---|---|---|
| Arabidopsis thaliana | AT4G26910 | Dihydrolipoamide succinyltransferase |
| Arabidopsis thaliana | AT5G55070 | dihydrolipoyllysine-residue succinyltransferase component of 2-oxoglutarate dehydrogenase complex 1 |
| Babesia bovis | BBOV_IV004840 | dihydrolipoamide succinyltransferase, putative |
| Brugia malayi | Bm1_34630 | dihydrolipoamide succinyltransferase |
| Brugia malayi | Bm1_34625 | Dihydrolipoyllysine-residue succinyltransferase component of 2-oxoglutarate dehydrogenase complex, mitochondrial precursor, puta |
| Candida albicans | CaO19.13545 | Dihydrolipoamide S-succinyltransferase |
| Candida albicans | CaO19.6126 | Dihydrolipoamide S-succinyltransferase |
| Caenorhabditis elegans | CELE_W02F12.5 | Protein DLST-1 |
| Chlamydia trachomatis | CT_055 | dihydrolipoamide succinyltransferase |
| Dictyostelium discoideum | DDB_G0275029 | 2-oxoglutarate dehydrogenase E2 component |
| Drosophila melanogaster | Dmel_CG5214 | CG5214 gene product from transcript CG5214-RA |
| Escherichia coli | b0727 | dihydrolipoyltranssuccinase |
| Echinococcus granulosus | EgrG_000851500 | dihydrolipoyllysine residue succinyltransferase |
| Echinococcus multilocularis | EmuJ_000851500 | dihydrolipoyllysine residue succinyltransferase |
| Homo sapiens | ENSG00000119689 | dihydrolipoamide S-succinyltransferase (E2 component of 2-oxo-glutarate complex) |
| Leishmania braziliensis | LbrM.28.2620 | 2-oxoglutarate dehydrogenase, E2 component, dihydrolipoamide succinyltransferase, putative |
| Leishmania donovani | LdBPK_282600.1 | 2-oxoglutarate dehydrogenase, E2 component, dihydrolipoamide succinyltransferase, putative |
| Leishmania infantum | LinJ.28.2600 | 2-oxoglutarate dehydrogenase, E2 component, dihydrolipoamide succinyltransferase, putative |
| Leishmania major | LmjF.28.2420 | 2-oxoglutarate dehydrogenase, E2 component, dihydrolipoamide succinyltransferase, putative |
| Leishmania mexicana | LmxM.28.2420 | 2-oxoglutarate dehydrogenase, E2 component, dihydrolipoamide succinyltransferase, putative |
| Loa Loa (eye worm) | LOAG_04620 | hypothetical protein |
| Loa Loa (eye worm) | LOAG_04619 | hypothetical protein |
| Mycobacterium leprae | ML0861c | Dihydrolipoamide succinyltransferase component of 2-oxoglutarate dehydrogenase complex SucB |
| Mus musculus | ENSMUSG00000004789 | dihydrolipoamide S-succinyltransferase (E2 component of 2-oxo-glutarate complex) |
| Mycobacterium tuberculosis | Rv2215 | DlaT, dihydrolipoamide acyltransferase, E2 component of pyruvate dehydrogenase |
| Mycobacterium ulcerans | MUL_3575 | dihydrolipoamide acetyltransferase |
| Neospora caninum | NCLIV_061040 | hypothetical protein |
| Oryza sativa | 4335689 | Os04g0394200 |
| Onchocerca volvulus | OVOC4905 |
|
| Plasmodium berghei | PBANKA_1419100 | dihydrolipoyllysine-residue succinyltransferase component of 2-oxoglutarate dehydrogenase complex, putative |
| Plasmodium falciparum | PF3D7_1320800 | dihydrolipoyllysine-residue succinyltransferase component of 2-oxoglutarate dehydrogenase complex |
| Plasmodium knowlesi | PKNH_1421400 | dihydrolipoyllysine-residue succinyltransferase component of 2-oxoglutarate dehydrogenase complex, putative |
| Plasmodium vivax | PVX_122850 | dihydrolipoyllysine-residue succinyltransferase component of 2-oxoglutarate dehydrogenase complex, putative |
| Plasmodium yoelii | PY03521 | 2-oxoglutarate dehydrogenase, E2 component, dihydrolipoamide succinyltransferase, putative |
| Saccharomyces cerevisiae | YDR148C | alpha-ketoglutarate dehydrogenase KGD2 |
| Schistosoma japonicum | Sjp_0112430 | ko:K00658 2-oxoglutarate dehydrogenase E2 component (dihydrolipoamide [EC2.3.1.61], putative |
| Schistosoma mansoni | Smp_104330 | dihydrolipoamide succinyltransferase component of 2-oxoglutarate dehydrogenase |
| Schmidtea mediterranea | mk4.000008.00 | Dihydrolipoyllysine-residue succinyltransferase component of 2-oxoglutarate dehydrogenase complex, mitochondrial |
| Trypanosoma brucei gambiense | Tbg972.11.13100 | 2-oxoglutarate dehydrogenase, E2 component, dihydrolipoamide succinyltransferase, putative |
| Trypanosoma brucei | Tb927.11.11680 | 2-oxoglutarate dehydrogenase E2 component, putative |
| Trypanosoma congolense | TcIL3000.11.12290 | 2-oxoglutarate dehydrogenase E2 component, putative |
| Trypanosoma cruzi | TcCLB.506025.60 | 2-oxoglutarate dehydrogenase, E2 component, dihydrolipoamide succinyltransferase, putative |
| Trypanosoma cruzi | TcCLB.503935.20 | 2-oxoglutarate dehydrogenase, E2 component, dihydrolipoamide succinyltransferase, putative |
| Toxoplasma gondii | TGME49_219550 | dihydrolipoyllysine-residue succinyltransferase component of oxoglutarate dehydrogenase |
| Theileria parva | TP01_0262 | dihydrolipoamide succinyltransferase, putative |
| Wolbachia endosymbiont of Brugia malayi | Wbm0108 | dihydrolipoamide acyltransferase E2 component |
Essentiality
| Gene/Ortholog | Organism | Phenotype | Source Study |
|---|---|---|---|
| Tb11.01.3550 | Trypanosoma brucei | significant loss of fitness in bloodstream forms (3 days) | alsford |
| Tb11.01.3550 | Trypanosoma brucei | significant loss of fitness in bloodstream forms (6 days) | alsford |
| Tb11.01.3550 | Trypanosoma brucei | significant loss of fitness in procyclic forms | alsford |
| Tb11.01.3550 | Trypanosoma brucei | significant loss of fitness in differentiation of procyclic to bloodstream forms | alsford |
| b0727 | Escherichia coli | essential | goodall |
| CELE_W02F12.5 | Caenorhabditis elegans | embryonic lethal | wormbase |
| CELE_W02F12.5 | Caenorhabditis elegans | larval arrest | wormbase |
| CELE_W02F12.5 | Caenorhabditis elegans | slow growth | wormbase |
| CELE_W02F12.5 | Caenorhabditis elegans | sterile | wormbase |
| PBANKA_1419100 | Plasmodium berghei | Dispensable | plasmo |
| TGME49_219550 | Toxoplasma gondii | Probably essential | sidik |
-
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 -
yeastgenome Systematic deletion of yeast genes Saccharomyces Genome Database -
shigen Profiling of E. coli Chromosome (PEC) National Institute of Genetics, Japan -
blattner Systematic mutagenesis of the E. coli (MG1655) genome J Bacteriol 2004, 186:4921-4930 -
wormbase C. elegans RNAi experiments WormBase web site, http://www.wormbase.org, release WS170 -
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
Phenotypes and Validation (curated)
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
Associated compounds / Druggability
Known modulators for this target
52 chemical compounds are associated with this genePredicted associations
By orthology with druggable targets
By sequence similarity to non orthologous druggable targets
Obtained from network model
Assayability
Assay information
- Inhibition Assay BINDINGDB
- Inhibition Assay. Mtb PDH (Lpd+DlaT+AceE) is provided by Dr. Bryk Ruslana. The assay was performed in a manner similar to that described in Bryk et al., Biochemistry (2010) 49.1616-1627 and modified for an online robotics screening system.A solution containing PDH (Lpd=15 ¿M; DlaT=30 ¿M; AceE=15 ¿M) was diluted 2-fold in 100 mM of potassium phosphate buffer (pH 7.0) for the assay. Another reaction solution containing 50 mM potassium phosphate buffer (pH 7.0), 200 ¿M TPP, 2 mM Pyruvate, 200 ¿M CoA, 1 mM MgCl2, 1 mM NAD+ was prepared. 5 ¿L/well of PDH solution was dispensed into 1536-well black plates. Next, 50 nL of each test compound (1 mM dissolved in DMSO) was added into each well. After 30 minutes of incubation, 5 ¿L/well of reaction solution was added. At the 30th minutes of the reaction, the florescence signal (excitation 360 nm and emission 460 nm) was obtained by Viewlux reader (PerkinElmer)
Reagent availability
Bibliographic References