Rv0819 (mshD)

Current annotations:
- TBCAP: (community-based annotations - see table at bottom of page)
- TBDB: mycothiol acetyltransferase
- REFSEQ: hypothetical protein
- PATRIC: Acetyl-CoA:Cys-GlcN-Ins acetyltransferase mycothiol synthase MshD
- TUBERCULIST: GCN5-related N-acetyltransferase MshD
- NCBI: GCN5-related N-acetyltransferase, MshD
- updated information (H37Rv4):
  - gene name: mshD
  - function:
  - reference:
Type: Essential
Start: 911736
End: 912683
Operon:

Trans-membrane region:
Role: V - Conserved hypotheticals
GO terms:
- GO:0071468 - cellular response to acidic pH (Uniprot)
- GO:0070301 - cellular response to hydrogen peroxide (Uniprot)
- GO:0044119 - growth of symbiont in host cell (Uniprot)
- GO:0035447 - mycothiol synthase activity (Uniprot)
- GO:0016747 - transferase activity, transferring acyl groups other than amino-acyl groups (Uniprot)
- GO:0016746 - transferase activity, transferring acyl groups (Uniprot)
- GO:0016740 - transferase activity (Uniprot)
- GO:0010126 - mycothiol metabolic process (Uniprot)
- GO:0010125 - mycothiol biosynthetic process (Uniprot)
- GO:0008080 - N-acetyltransferase activity (Uniprot)
- GO:0005829 - cytosol (Uniprot)
Reaction(s) (based on iSM810 metabolic model):
- ACCOA[c] + CYS_NG_INS[c] -> COA[c] + MYCOTHIOL[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: 1p0h, 1ozp, 2c27
Search for Homologs in PDB

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

PDB	aa ident	species	PDB title
2C27	99%	MYCOBACTERIUM TUBERCULOSIS	The Structure of Mycothiol Synthase in Complex with des- AcetylMycothiol and CoenzymeA.
1P0H	99%	Mycobacterium tuberculosis	Crystal Structure of Rv0819 from Mycobacterium Tuberculosis MshD-Mycothiol Synthase Coenzyme A Complex
1OZP	99%	Mycobacterium tuberculosis	Crystal Structure of Rv0819 from Mycobacterium tuberculosis MshD-Mycothiol Synthase Acetyl-Coenzyme A Complex.

Links to additional information on mshD:
- KEGG - nucleotide and amino acid sequences of gene
- Mycobrowser
- PATRIC
- BioCyc
- Systems Biology
- TBDB (updated)
- Phyre2 structure prediction, model: final.casp.pdb (from Mao et al, 2013)
- UniProt
- AlphaFold model
- Vulnerability = -0.1 (from Jeremy Rock's lab)

Amino Acid Sequence

VTALDWRSALTADEQRSVRALVTATTAVDGVAPVGEQVLRELGQQRTEHLLVAGSRPGGPIIGYLNLSPPRGAGGAMAELVVHPQSRRRGIGTAMARAAL
AKTAGRNQFWAHGTLDPARATASALGLVGVRELIQMRRPLRDIPEPTIPDGVVIRTYAGTSDDAELLRVNNAAFAGHPEQGGWTAVQLAERRGEAWFDPD
GLILAFGDSPRERPGRLLGFHWTKVHPDHPGLGEVYVLGVDPAAQRRGLGQMLTSIGIVSLARRLGGRKTLDPAVEPAVLLYVESDNVAAVRTYQSLGFT
TYSVDTAYALAGTDN

(Nucleotide sequence available on KEGG)

Additional Information

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
Non-Essential	Sodium Oleate	H37RvMA	Gumbel	Subhalaxmi Nambi	Probability of Essentiality: 0.000000; 3 non-insertions in a row out of 14 sites
Non-Essential	Lignoceric Acid	H37RvMA	Gumbel	Subhalaxmi Nambi	Probability of Essentiality: 0.000200; 3 non-insertions in a row out of 14 sites
Uncertain	Phosphatidylcholine	H37RvMA	Gumbel	Subhalaxmi Nambi	Probability of Essentiality: 0.497000; 5 non-insertions in a row out of 14 sites
Essential	minimal media + 0.1% glycerol	H37RvMA	Gumbel	Griffin et al. (2011)	Probability of Essentiality: 0.999850; 12 non-insertions in a row out of 14 sites
Uncertain	minimal media + 0.01% cholesterol	H37RvMA	Gumbel	Griffin et al. (2011)	Probability of Essentiality: 0.257500; 4 non-insertions in a row out of 14 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: 1.78
Growth-Advantage	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:
- No bindings to other targets were found.

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
Term	TBRXN:MSHS mycothiol synthase - IDA	njamshidi	IDA	\|12754249\|12930994	see PMID: 12754249, 12930994, Cole et al text MW. Vetting, SL. Roderick et al. Crystal structure of mycothiol synthase (Rv0819) from Mycobacterium tuberculosis shows structural homology to the GNAT family of N-acetyltransferases. Protein Sci. 2003
Citation	The glycosyltransferase gene encoding the enzyme catalyzing the first step of mycothiol biosynthesis (mshA). GL. Newton, T. Koledin et al. J. Bacteriol. 2003	njamshidi	ISS	\|12754249\|12930994	see PMID: 12754249, 12930994, Cole et al text
Term	TBRXN:MSHS mycothiol synthase - ISS	njamshidi	ISS	\|12754249\|12930994	see PMID: 12754249, 12930994, Cole et al text GL. Newton, T. Koledin et al. The glycosyltransferase gene encoding the enzyme catalyzing the first step of mycothiol biosynthesis (mshA). J. Bacteriol. 2003
Citation	Crystal structure of mycothiol synthase (Rv0819) from Mycobacterium tuberculosis shows structural homology to the GNAT family of N-acetyltransferases. MW. Vetting, SL. Roderick et al. Protein Sci. 2003	njamshidi	ISS	\|12754249\|12930994	see PMID: 12754249, 12930994, Cole et al text
Term	TBRXN:MSHS mycothiol synthase - ISS	njamshidi	ISS	\|12754249\|12930994	see PMID: 12754249, 12930994, Cole et al text MW. Vetting, SL. Roderick et al. Crystal structure of mycothiol synthase (Rv0819) from Mycobacterium tuberculosis shows structural homology to the GNAT family of N-acetyltransferases. Protein Sci. 2003
Citation	The glycosyltransferase gene encoding the enzyme catalyzing the first step of mycothiol biosynthesis (mshA). GL. Newton, T. Koledin et al. J. Bacteriol. 2003	njamshidi	IDA	\|12754249\|12930994	see PMID: 12754249, 12930994, Cole et al text
Term	TBRXN:MSHS mycothiol synthase - IDA	njamshidi	IDA	\|12754249\|12930994	see PMID: 12754249, 12930994, Cole et al text GL. Newton, T. Koledin et al. The glycosyltransferase gene encoding the enzyme catalyzing the first step of mycothiol biosynthesis (mshA). J. Bacteriol. 2003
Citation	Crystal structure of mycothiol synthase (Rv0819) from Mycobacterium tuberculosis shows structural homology to the GNAT family of N-acetyltransferases. MW. Vetting, SL. Roderick et al. Protein Sci. 2003	njamshidi	IDA	\|12754249\|12930994	see PMID: 12754249, 12930994, Cole et al text
Citation	The glycosyltransferase gene encoding the enzyme catalyzing the first step of mycothiol biosynthesis (mshA). GL. Newton, T. Koledin et al. J. Bacteriol. 2003	jjmcfadden		12754249	Inferred from direct assay
Other	EC:	jjmcfadden			Inferred from direct assay GL. Newton, T. Koledin et al. The glycosyltransferase gene encoding the enzyme catalyzing the first step of mycothiol biosynthesis (mshA). J. Bacteriol. 2003
Citation	Crystal structure of mycothiol synthase (Rv0819) from Mycobacterium tuberculosis shows structural homology to the GNAT family of N-acetyltransferases. MW. Vetting, SL. Roderick et al. Protein Sci. 2003	extern:JZUCKER		12930994	Assay of protein purified to homogeneity
Term	EC:2.3.1.189 Mycothiol synthase. - NR	extern:JZUCKER	NR		Assay of protein purified to homogeneity MW. Vetting, SL. Roderick et al. Crystal structure of mycothiol synthase (Rv0819) from Mycobacterium tuberculosis shows structural homology to the GNAT family of N-acetyltransferases. Protein Sci. 2003

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