Rv2965c (kdtB)

Current annotations:
- TBCAP: (community-based annotations - see table at bottom of page)
- TBDB: phosphopantetheine adenylyltransferase
- REFSEQ: phosphopantetheine adenylyltransferase
- PATRIC: Phosphopantetheine adenylyltransferase (EC 2.7.7.3)
- TUBERCULIST: Probable phosphopantetheine adenylyltransferase KdtB (pantetheine- phosphate adenylyltransferase) (PPAT) (dephospho-CoA pyrophosphorylase)
- NCBI: Probable phosphopantetheine adenylyltransferase KdtB (pantetheine-phosphate adenylyltransferase) (PPAT) (dephospho-CoA pyrophosphorylase)
- updated information (H37Rv4):
  - gene name: coaD/kdtB
  - function:
  - reference: Evans (2016) PMID: 27676316
Type: Not Target
Start: 3318330
End: 3318815
Operon:

Trans-membrane region:
Role: II.C.2 - Surface polysaccharides, lipopolysaccharides, proteins and antigens
GO terms:
- GO:0034214 - protein hexamerization (Uniprot)
- GO:0016779 - nucleotidyltransferase activity (Uniprot)
- GO:0016740 - transferase activity (Uniprot)
- GO:0015937 - coenzyme A biosynthetic process (Uniprot)
- GO:0009058 - biosynthetic process (Uniprot)
- GO:0005737 - cytoplasm (Uniprot)
- GO:0005524 - ATP binding (Uniprot)
- GO:0004595 - pantetheine-phosphate adenylyltransferase activity (Uniprot)
- GO:0003824 - catalytic activity (Uniprot)
- GO:0000166 - nucleotide binding (Uniprot)
Reaction(s) (based on iSM810 metabolic model):
- ATP[c] + 4PPNTE[c] -> PPI[c] + DPCOA[c]
Gene Expression Profile (Transcriptional Responses to Drugs; Boshoff et al, 2004)
Gene Modules extracted from cluster analysis of 249 transcriptomic datasets using ICA
Orthologs among selected mycobacteria
Protein structure: 3nbk, 3lcj, 3pnb, 3rff, 3nba, 3rba, 4e1a, 3rhs, 1tfu, 3uc5
Search for Homologs in PDB

Top 10 Homologs in PDB (as of Nov 2020):

PDB	aa ident	species	PDB title
6QMI	100%	Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)	Phosphopantetheine adenylyltransferase from Mycobacterium tuberculosis in complex with 3-(1H-indol-1-yl)propanoic acid at 1.7A resolution.
6QMH	100%	Mycobacterium tuberculosis	Phosphopantetheine adenylyltransferase from Mycobacterium tuberculosis in complex with 3-(1H-indol-3-yl)propanoic acid at 1.6A resolution.
6QMG	100%	Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)	Phosphopantetheine adenylyltransferase from Mycobacterium tuberculosis in complex with 5-methyl-1-phenyl-1H-pyrazole-4-carboxylic acid at 1.8A resolution.
6QMF	100%	Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)	Phosphopantetheine adenylyltransferase from Mycobacterium tuberculosis in complex with 5-[3-(1H-indol-3-yl)propoxy]-1-phenyl-1H-pyrazole-4-carboxylic acid at 1.8A resolution.
6G7V	100%	Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)	Phosphopantetheine adenylyltransferase from Mycobacterium tuberculosis in complex with 5-methyl-1-phenyl-1H-pyrazole-4-carboxylic acid at 1.8A resolution.
6G7U	100%	Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)	Phosphopantetheine adenylyltransferase from Mycobacterium tuberculosis in complex with 5-[3-(1H-indol-3-yl)propoxy]-1-phenyl-1H-pyrazole-4-carboxylic acid at 1.8A resolution.
6G7T	100%	Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)	Phosphopantetheine adenylyltransferase from Mycobacterium tuberculosis in complex with 3-(1H-indol-3-yl)propanoic acid at 1.6A resolution.
6G7S	100%	Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)	Phosphopantetheine adenylyltransferase from Mycobacterium tuberculosis in complex with 3-(1H-indol-1-yl)propanoic acid at 1.7A resolution.
6G6V	100%	Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)	Phosphopantetheine adenylyltransferase from Mycobacterium tuberculosis in complex with 4-(2-carboxybenzoyl)-2-nitrobenzoic acid at 1.9A resolution.
4R0N	100%	Mycobacterium tuberculosis BT1	Hexagonal form of phosphopantetheine adenylyltransferase from Mycobacterium tuberculosis

Links to additional information on kdtB:
- TBDB (updated)
- Phyre2 structure prediction, model: final.casp.pdb (from Mao et al, 2013)
- UniProt
- AlphaFold model
- Vulnerability = -9.367 (from Jeremy Rock's lab)
- KEGG - nucleotide and amino acid sequences of gene
- Mycobrowser
- PATRIC
- BioCyc
- Systems Biology

Amino Acid Sequence

MTGAVCPGSFDPVTLGHVDIFERAAAQFDEVVVAILVNPAKTGMFDLDERIAMVKESTTHLPNLRVQVGHGLVVDFVRSCGMTAIVKGLRTGTDFEYELQ
MAQMNKHIAGVDTFFVATAPRYSFVSSSLAKEVAMLGGDVSELLPEPVNRRLRDRLNTERT

(Nucleotide sequence available on KEGG)

Additional Information

CoaD

ESSENTIALITY

MtbTnDB - interactive tool for exploring a database of published TnSeq datasets for Mtb

TnSeqCorr - genes with correlated TnSeq profiles across >100 conditions *new*

Classification	Condition	Strain	Method	Reference	Notes
Uncertain	Sodium Oleate	H37RvMA	Gumbel	Subhalaxmi Nambi	Probability of Essentiality: 0.876100; 4 non-insertions in a row out of 4 sites
Uncertain	Lignoceric Acid	H37RvMA	Gumbel	Subhalaxmi Nambi	Probability of Essentiality: 0.935650; 4 non-insertions in a row out of 4 sites
Uncertain	Phosphatidylcholine	H37RvMA	Gumbel	Subhalaxmi Nambi	Probability of Essentiality: 0.943650; 4 non-insertions in a row out of 4 sites
Uncertain	minimal media + 0.1% glycerol	H37RvMA	Gumbel	Griffin et al. (2011)	Probability of Essentiality: 0.760300; 4 non-insertions in a row out of 5 sites
Uncertain	minimal media + 0.01% cholesterol	H37RvMA	Gumbel	Griffin et al. (2011)	Probability of Essentiality: 0.755150; 4 non-insertions in a row out of 5 sites
Non-Essential	7H10-glycerol	H37RvMA	TraSH	Sassetti et al. (2003a)
Non-Essential	C57BL/6J mice (8 weeks)	H37RvMA	TraSH	Sassetti et al. (2003b)	Hybridization Ratio: 0.68
Non-Essential	7H09/7H10 + rich media	H37RvMA	MotifHMM	DeJesus et al. (2017)	Fully saturated (14 reps).

TnSeq Data No data currently available.

No TnSeq data currently available for this Target.

RNASeq Data No data currently available.

No RNA-Seq data currently available for this Target.

Metabolomic Profiles No data currently available.

No Metabolomic data currently available for this Target.

Proteomic Data No data currently available.

No Proteomic data currently available for this Target.

Regulatory Relationships from Systems Biology

BioCyc

Gene interactions based on ChIPSeq and Transcription Factor Over-Expression (TFOE) (Systems Biology)

NOTE: Green edges represent the connected genes being classified as differentially essential as a result of the middle gene being knocked out. These interactions are inferred based on RNASeq.

Interactions based on ChIPSeq data

RNA processing and modification

Energy production and conversion

Chromatin structure and dynamics

Amino acid transport and metabolism

Cell cycle control, cell division, chromosome partitioning

Carbohydrate transport and metabolism

Nucleotide transport and metabolism

Lipid transport and metabolism

Coenzyme transport and metabolism

Transcription

Translation, ribosomal structure and biogenesis

Cell wall/membrane/envelope biogenesis

Replication, recombination and repair

Posttranslational modification, protein turnover, chaperones

Cell motility

Secondary metabolites biosynthesis, transport and catabolism

Inorganic ion transport and metabolism

Function unknown

General function prediction only

Intracellular trafficking, secretion, and vesicular transport

Signal transduction mechanisms

Extracellular structures

Defense mechanisms

Nuclear structure

Cytoskeleton

BioCyc Co-regulated genes based on gene expression profiling (Systems Biology, Inferelator Network)

Differentially expressed as result of RNASeq in glycerol environment (Only top 20 genes shown sorted by log fold change with p_adj 0.05).

Conditionally essential as result of TNSeq (Only top 20 genes shown sorted by log fold change with p_adj 0.05).

BioCyc Transcription factor binding based on ChIP-Seq (Systems Biology)

Binds To:
- No bindings to other targets were found.
Bound By:
- No bindings from other targets were found.

Interactions based on ChIPSeq data (Minch et al. 2014)

Binds To:
- No bindings to other targets were found.
Bound By:
- Rv3133c (devR) (Direct binding)
- Rv3736 (-) (Direct binding)

Interactions based on TFOE data (Rustad et al. 2014)

Upregulates:
- Does not upregulate other genes.
Upregulated by:
- Not upregulated by other genes.
Downregulates:
- Does not downregulate other genes.
Downregulated by:
- Not downregulated by other genes.

Property	Value	Creator	Evidence	PMID	Comment
Symbol	kdtB	jevans			Ligand binding results in asymmetry and alters the structure of the solvent channel - ligand binding restricted to one tetramer of the symmetrical hexamer VK. Morris,T. Izard Substrate-induced asymmetry and channel closure revealed by the apoenzyme structure of Mycobacterium tuberculosis phosphopantetheine adenylyltransferase. Protein Sci. 2004
Citation	Substrate-induced asymmetry and channel closure revealed by the apoenzyme structure of Mycobacterium tuberculosis phosphopantetheine adenylyltransferase. VK. Morris,T. Izard Protein Sci. 2004	jevans		15322293	Ligand binding results in asymmetry and alters the structure of the solvent channel - ligand binding restricted to one tetramer of the symmetrical hexamer
Symbol	kdtB	jevans			CoA only binds Mtb PPAT in one conformation authors,T. Wubben,AD. Mesecar Structure of Mycobacterium tuberculosis phosphopantetheine adenylyltransferase in complex with the feedback inhibitor CoA reveals only one active-site conformation. Acta Crystallogr. Sect. F Struct. Biol. Cryst. Commun. 2011
Citation	Structure of Mycobacterium tuberculosis phosphopantetheine adenylyltransferase in complex with the feedback inhibitor CoA reveals only one active-site conformation. authors,T. Wubben,AD. Mesecar Acta Crystallogr. Sect. F Struct. Biol. Cryst. Commun. 2011	jevans		21543857	CoA only binds Mtb PPAT in one conformation
Citation	Rhombohedral crystals of Mycobacterium tuberculosis phosphopantetheine adenylyltransferase. KL. Brown, VK. Morris et al. Acta Crystallogr. D Biol. Crystallogr. 2004	jjmcfadden		14684928	Inferred from direct assay
Term	EC:2.7.7.3 Pantetheine-phosphate adenylyltransferase. - NR	jjmcfadden	NR		Inferred from direct assay KL. Brown, VK. Morris et al. Rhombohedral crystals of Mycobacterium tuberculosis phosphopantetheine adenylyltransferase. Acta Crystallogr. D Biol. Crystallogr. 2004

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