Rv0391 (metZ)

Current annotations:
- TBCAP: (community-based annotations - see table at bottom of page)
- TBDB: O-succinylhomoserine sulfhydrylase
- REFSEQ: O-succinylhomoserine sulfhydrylase
- PATRIC: O-acetylhomoserine sulfhydrylase (EC 2.5.1.49)
- TUBERCULIST: Probable O-succinylhomoserine sulfhydrylase MetZ (OSH sulfhydrylase)
- NCBI: Probable O-succinylhomoserine sulfhydrylase MetZ (OSH sulfhydrylase)
- updated information (H37Rv4):
  - gene name: metZ
  - function:
  - reference:
Type: Not Target
Start: 470010
End: 471230
Operon:

Trans-membrane region:
Role: I.D.2 - Aspartate family
GO terms:
- GO:0071268 - homocysteine biosynthetic process (Uniprot)
- GO:0030170 - pyridoxal phosphate binding (Uniprot)
- GO:0016740 - transferase activity (Uniprot)
- GO:0009086 - methionine biosynthetic process (Uniprot)
- GO:0008652 - cellular amino acid biosynthetic process (Uniprot)
- GO:0004123 - cystathionine gamma-lyase activity (Uniprot)
- GO:0003962 - cystathionine gamma-synthase activity (Uniprot)
- GO:0003824 - catalytic activity (Uniprot)
Reaction(s) (based on iSM810 metabolic model):
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: 3ndn
Search for Homologs in PDB

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

PDB	aa ident	species	PDB title
3NDN	100%	Mycobacterium tuberculosis	Crystal structure of O-succinylhomoserine sulfhydrylase from Mycobacterium tuberculosis covalently bound to pyridoxal-5-phosphate
6S0C	40%	Citrobacter freundii	Crystal structure of methionine gamma-lyase from Citrobacter freundii modified by dimethylthiosulfinate
6EGR	40%	Citrobacter freundii	Crystal structure of Citrobacter freundii methionine gamma-lyase with V358Y replacement
5M3Z	40%	Citrobacter freundii	Crystal structure of Citrobacter freundii methionine gamma-lyase with C115H replacement in the complex with L-norleucine
5K30	40%	Citrobacter freundii	Crystal structure of methionine gamma-lyase from Citrobacter freundii modified by S-Ethyl-L-cysteine sulfoxide
5E4Z	40%	Citrobacter freundii	Crystal structure of methionine gamma-lyase from Citrobacter freundii with C115A substitution
5D5S	40%	Citrobacter freundii	Crystal structure of methionine gamma-lyase from Citrobacter freundii, S339A mutant
4OMA	40%	Citrobacter freundii	The crystal structure of methionine gamma-lyase from Citrobacter freundii in complex with L-cycloserine pyridoxal-5'-phosphate
4MKK	40%	Citrobacter freundii	Crystal structure of C115A mutant L-methionine gamma-lyase from Citrobacter freundii modified by allicine
4MKJ	40%	Citrobacter freundii	Crystal structure of L-methionine gamma-lyase from Citrobacter freundii modified by allicine

Links to additional information on metZ:
- TBDB (updated)
- Phyre2 structure prediction, model: final.casp.pdb (from Mao et al, 2013)
- UniProt
- AlphaFold model
- Vulnerability = 0.205 (from Jeremy Rock's lab)
- KEGG - nucleotide and amino acid sequences of gene
- Mycobrowser
- PATRIC
- BioCyc
- Systems Biology

Amino Acid Sequence

MTDESSVRTPKALPDGVSQATVGVRGGMLRSGFEETAEAMYLTSGYVYGSAAVAEKSFAGELDHYVYSRYGNPTVSVFEERLRLIEGAPAAFATASGMAA
VFTSLGALLGAGDRLVAARSLFGSCFVVCSEILPRWGVQTVFVDGDDLSQWERALSVPTQAVFFETPSNPMQSLVDIAAVTELAHAAGAKVVLDNVFATP
LLQQGFPLGVDVVVYSGTKHIDGQGRVLGGAILGDREYIDGPVQKLMRHTGPAMSAFNAWVLLKGLETLAIRVQHSNASAQRIAEFLNGHPSVRWVRYPY
LPSHPQYDLAKRQMSGGGTVVTFALDCPEDVAKQRAFEVLDKMRLIDISNNLGDAKSLVTHPATTTHRAMGPEGRAAIGLGDGVVRISVGLEDTDDLIAD
IDRALS

(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
Uncertain	Sodium Oleate	H37RvMA	Gumbel	Subhalaxmi Nambi	Probability of Essentiality: 0.345100; 6 non-insertions in a row out of 21 sites
Uncertain	Lignoceric Acid	H37RvMA	Gumbel	Subhalaxmi Nambi	Probability of Essentiality: 0.667950; 6 non-insertions in a row out of 21 sites
Uncertain	Phosphatidylcholine	H37RvMA	Gumbel	Subhalaxmi Nambi	Probability of Essentiality: 0.722400; 6 non-insertions in a row out of 21 sites
Uncertain	minimal media + 0.1% glycerol	H37RvMA	Gumbel	Griffin et al. (2011)	Probability of Essentiality: 0.600050; 6 non-insertions in a row out of 22 sites
Essential	minimal media + 0.01% cholesterol	H37RvMA	Gumbel	Griffin et al. (2011)	Probability of Essentiality: 1.000000; 15 non-insertions in a row out of 22 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: 0.33
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

Binds To:
- No bindings to other targets were found.
Bound By:
- Rv0022c (whiB5)
- Rv2250c (-)

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

Binds To:
- No bindings to other targets were found.
Bound By:
- Rv0081 (-) (Upstream of operon)
- Rv0678 (-) (Upstream of operon)
- Rv1033c (trcR) (Upstream of operon)
- Rv3765c (tcrX) (Upstream of operon)

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

Upregulates:
- Does not upregulate other genes.
Upregulated by:
- Rv0022c (whiB5)
Downregulates:
- Does not downregulate other genes.
Downregulated by:
- Rv2250c (-)

Property	Value	Creator	Evidence	PMID	Comment
Citation	Functional demonstration of reverse transsulfuration in the Mycobacterium tuberculosis complex reveals that methionine is the preferred sulfur source for pathogenic Mycobacteria. PR. Wheeler, NG. Coldham et al. J. Biol. Chem. 2005	njamshidi	IDA	15576367	Reversible - PMID: 15576367. Recycle sulfur from cysteine (not methionine)
Term	EC:4.2.99.9 Transferred entry: 2.5.1.48. - IDA	njamshidi	IDA	15576367	Reversible - PMID: 15576367. Recycle sulfur from cysteine (not methionine) PR. Wheeler, NG. Coldham et al. Functional demonstration of reverse transsulfuration in the Mycobacterium tuberculosis complex reveals that methionine is the preferred sulfur source for pathogenic Mycobacteria. J. Biol. Chem. 2005
Term	TBRXN:SHSL1r O-succinylhomoserine lyase reversible - IDA	njamshidi	IDA	15576367	Reversible - PMID: 15576367. Recycle sulfur from cysteine (not methionine) PR. Wheeler, NG. Coldham et al. Functional demonstration of reverse transsulfuration in the Mycobacterium tuberculosis complex reveals that methionine is the preferred sulfur source for pathogenic Mycobacteria. J. Biol. Chem. 2005
Citation	Functional demonstration of reverse transsulfuration in the Mycobacterium tuberculosis complex reveals that methionine is the preferred sulfur source for pathogenic Mycobacteria. PR. Wheeler, NG. Coldham et al. J. Biol. Chem. 2005	njamshidi	ISS	15576367	Reversible - PMID: 15576367. Recycle sulfur from cysteine (not methionine)
Term	EC:4.2.99.9 Transferred entry: 2.5.1.48. - ISS	njamshidi	ISS	15576367	Reversible - PMID: 15576367. Recycle sulfur from cysteine (not methionine) PR. Wheeler, NG. Coldham et al. Functional demonstration of reverse transsulfuration in the Mycobacterium tuberculosis complex reveals that methionine is the preferred sulfur source for pathogenic Mycobacteria. J. Biol. Chem. 2005
Term	TBRXN:SHSL1r O-succinylhomoserine lyase reversible - ISS	njamshidi	ISS	15576367	Reversible - PMID: 15576367. Recycle sulfur from cysteine (not methionine) PR. Wheeler, NG. Coldham et al. Functional demonstration of reverse transsulfuration in the Mycobacterium tuberculosis complex reveals that methionine is the preferred sulfur source for pathogenic Mycobacteria. J. Biol. Chem. 2005
Citation	Functional demonstration of reverse transsulfuration in the Mycobacterium tuberculosis complex reveals that methionine is the preferred sulfur source for pathogenic Mycobacteria. PR. Wheeler, NG. Coldham et al. J. Biol. Chem. 2005	njamshidi	IPI	15576367	Reversible - PMID: 15576367. Recycle sulfur from cysteine (not methionine)
Term	EC:4.2.99.9 Transferred entry: 2.5.1.48. - IPI	njamshidi	IPI	15576367	Reversible - PMID: 15576367. Recycle sulfur from cysteine (not methionine) PR. Wheeler, NG. Coldham et al. Functional demonstration of reverse transsulfuration in the Mycobacterium tuberculosis complex reveals that methionine is the preferred sulfur source for pathogenic Mycobacteria. J. Biol. Chem. 2005
Term	TBRXN:SHSL1r O-succinylhomoserine lyase reversible - IPI	njamshidi	IPI	15576367	Reversible - PMID: 15576367. Recycle sulfur from cysteine (not methionine) PR. Wheeler, NG. Coldham et al. Functional demonstration of reverse transsulfuration in the Mycobacterium tuberculosis complex reveals that methionine is the preferred sulfur source for pathogenic Mycobacteria. J. Biol. Chem. 2005
Citation	Comparative genomics of the vitamin B12 metabolism and regulation in prokaryotes. authors,DA. Rodionov,AG. Vitreschak,AA. Mironov,MS. Gelfand J. Biol. Chem. 2003	mwilliams		12869542	Predicted as nonorthologous functional replacement for cobF

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