Rv2987c (leuD)

Current annotations:
- TBCAP: (community-based annotations - see table at bottom of page)
- TBDB: 3-isopropylmalate dehydratase small subunit
- REFSEQ: isopropylmalate isomerase small subunit
- PATRIC: 3-isopropylmalate dehydratase small subunit (EC 4.2.1.33)
- TUBERCULIST: Probable 3-isopropylmalate dehydratase (small subunit) LeuD (isopropylmalate isomerase) (alpha-IPM isomerase) (IPMI)
- NCBI: Probable 3-isopropylmalate dehydratase (small subunit) LeuD (isopropylmalate isomerase) (alpha-IPM isomerase) (IPMI)
- updated information (H37Rv4):
  - gene name: leuD
  - function:
  - reference:
Type: Not Target
Start: 3344033
End: 3344629
Operon:

Trans-membrane region:
Role: I.D.7 - Branched amino acid family
GO terms:
- GO:0040007 - growth (Uniprot)
- GO:0016829 - lyase activity (Uniprot)
- GO:0009316 - 3-isopropylmalate dehydratase complex (Uniprot)
- GO:0009098 - leucine biosynthetic process (Uniprot)
- GO:0009082 - branched-chain amino acid biosynthetic process (Uniprot)
- GO:0008652 - cellular amino acid biosynthetic process (Uniprot)
- GO:0008152 - metabolic process (Uniprot)
- GO:0005886 - plasma membrane (Uniprot)
- GO:0003861 - 3-isopropylmalate dehydratase activity (Uniprot)
Reaction(s) (based on iSM810 metabolic model):
- IPPMAL[c] <=> CBHCAP[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: 3h5h, 3h5j, 3h5e
Search for Homologs in PDB

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

PDB	aa ident	species	PDB title
3H5J	100%	Mycobacterium tuberculosis	LeuD_1-168 small subunit of isopropylmalate isomerase (Rv2987c) from mycobacterium tuberculosis
3H5H	100%	Mycobacterium tuberculosis	LeuD_1-186 small subunit of isopropylmalate isomerase (Rv2987c) from mycobacterium tuberculosis
3H5E	99%	Mycobacterium tuberculosis	LeuD_1-156 small subunit of isopropylmalate isomerase (Rv2987c) from mycobacterium tuberculosis
3Q3W	41%	Campylobacter jejuni	Isopropylmalate isomerase small subunit from Campylobacter jejuni.
3VBA	41%	Methanocaldococcus jannaschii	Crystal structure of methanogen 3-isopropylmalate isomerase small subunit
2HCU	39%	Streptococcus mutans	Crystal Structure Of Smu.1381 (or LeuD) from Streptococcus Mutans
2PKP	36%	Methanocaldococcus jannaschii	Crystal structure of 3-isopropylmalate dehydratase (leuD)from Methhanocaldococcus Jannaschii DSM2661 (MJ1271)
1V7L	36%	Pyrococcus horikoshii	Structure of 3-isopropylmalate isomerase small subunit from Pyrococcus horikoshii

Links to additional information on leuD:
- Mycobrowser
- PATRIC
- TBDB (updated)
- Phyre2 structure prediction, model: final.casp.pdb (from Mao et al, 2013)
- UniProt
- AlphaFold model
- Vulnerability = -3.274 (from Jeremy Rock's lab)
- KEGG - nucleotide and amino acid sequences of gene
- BioCyc
- Systems Biology

Amino Acid Sequence

MEAFHTHSGIGVPLRRSNVDTDQIIPAVFLKRVTRTGFEDGLFAGWRSDPAFVLNLSPFDRGSVLVAGPDFGTGSSREHAVWALMDYGFRVVISSRFGDI
FRGNAGKAGLLAAEVAQDDVELLWKLIEQSPGLEITANLQDRIITAATVVLPFKIDDHSAWRLLEGLDDIALTLRKLDEIEAFEGACAYWKPRTLPAP

(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: 0.989950; 10 non-insertions in a row out of 10 sites
Essential	Lignoceric Acid	H37RvMA	Gumbel	Subhalaxmi Nambi	Probability of Essentiality: 0.999250; 10 non-insertions in a row out of 10 sites
Essential	Phosphatidylcholine	H37RvMA	Gumbel	Subhalaxmi Nambi	Probability of Essentiality: 0.999450; 10 non-insertions in a row out of 10 sites
Essential	minimal media + 0.1% glycerol	H37RvMA	Gumbel	Griffin et al. (2011)	Probability of Essentiality: 0.996600; 9 non-insertions in a row out of 10 sites
Essential	minimal media + 0.01% cholesterol	H37RvMA	Gumbel	Griffin et al. (2011)	Probability of Essentiality: 0.999200; 10 non-insertions in a row out of 10 sites
Essential	7H10-glycerol	H37RvMA	TraSH	Sassetti et al. (2003a)
Essential	C57BL/6J mice (8 weeks)	H37RvMA	TraSH	Sassetti et al. (2003b)	Hybridization Ratio: 0.06
Growth-Defect	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:

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

Binds To:
- No bindings to other targets were found.
Bound By:
- Rv1033c (trcR) (Direct binding)
- Rv1049 (-) (Upstream of operon)
- Rv1719 (-) (Upstream of operon)
- Rv2989 (-) (Upstream of operon)

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

Upregulates:
- Does not upregulate other genes.
Upregulated by:
- Rv0757 (phoP)
Downregulates:
- Does not downregulate other genes.
Downregulated by:

Property	Value	Creator	Evidence	PMID	Comment
Citation	Cloning, expression, purification, crystallization and preliminary X-ray diffraction analysis of the small subunit of isopropylmalate isomerase (Rv2987c) from Mycobacterium tuberculosis. M. Karuppasamy, A. Geerlof et al. Acta Crystallogr. Sect. F Struct. Biol. Cryst. Commun. 2009	kholia.trupti	NAS	19194004	Structural Analysis
Interaction	PhysicalInteraction Rv2988c	kholia.trupti	NAS		Structural Analysis M. Karuppasamy, A. Geerlof et al. Cloning, expression, purification, crystallization and preliminary X-ray diffraction analysis of the small subunit of isopropylmalate isomerase (Rv2987c) from Mycobacterium tuberculosis. Acta Crystallogr. Sect. F Struct. Biol. Cryst. Commun. 2009
Citation	Attenuation of and protection induced by a leucine auxotroph of Mycobacterium tuberculosis. MK. Hondalus, S. Bardarov et al. Infect. Immun. 2000	kholia.trupti	NAS	10768986	Spectrophotometric
Interaction	PhysicalInteraction Rv2988c	kholia.trupti	NAS		Spectrophotometric MK. Hondalus, S. Bardarov et al. Attenuation of and protection induced by a leucine auxotroph of Mycobacterium tuberculosis. Infect. Immun. 2000
Citation	Crystal structure of LeuA from Mycobacterium tuberculosis, a key enzyme in leucine biosynthesis. N. Koon, CJ. Squire et al. Proc. Natl. Acad. Sci. U.S.A. 2004	kholia.trupti	NAS	15159544	Spectrophotometric
Interaction	PhysicalInteraction Rv2988c	kholia.trupti	NAS		Spectrophotometric N. Koon, CJ. Squire et al. Crystal structure of LeuA from Mycobacterium tuberculosis, a key enzyme in leucine biosynthesis. Proc. Natl. Acad. Sci. U.S.A. 2004
Citation	Cloning, expression, purification, crystallization and preliminary X-ray diffraction analysis of the small subunit of isopropylmalate isomerase (Rv2987c) from Mycobacterium tuberculosis. M. Karuppasamy, A. Geerlof et al. Acta Crystallogr. Sect. F Struct. Biol. Cryst. Commun. 2009	kholia.trupti	NAS	19194004	Spectrophotometric
Interaction	PhysicalInteraction Rv2988c	kholia.trupti	NAS		Spectrophotometric M. Karuppasamy, A. Geerlof et al. Cloning, expression, purification, crystallization and preliminary X-ray diffraction analysis of the small subunit of isopropylmalate isomerase (Rv2987c) from Mycobacterium tuberculosis. Acta Crystallogr. Sect. F Struct. Biol. Cryst. Commun. 2009
Citation	Attenuation of and protection induced by a leucine auxotroph of Mycobacterium tuberculosis. MK. Hondalus, S. Bardarov et al. Infect. Immun. 2000	kholia.trupti	NAS	10768986	Structural Analysis
Interaction	PhysicalInteraction Rv2988c	kholia.trupti	NAS		Structural Analysis MK. Hondalus, S. Bardarov et al. Attenuation of and protection induced by a leucine auxotroph of Mycobacterium tuberculosis. Infect. Immun. 2000
Citation	Crystal structure of LeuA from Mycobacterium tuberculosis, a key enzyme in leucine biosynthesis. N. Koon, CJ. Squire et al. Proc. Natl. Acad. Sci. U.S.A. 2004	kholia.trupti	NAS	15159544	Structural Analysis
Interaction	PhysicalInteraction Rv2988c	kholia.trupti	NAS		Structural Analysis N. Koon, CJ. Squire et al. Crystal structure of LeuA from Mycobacterium tuberculosis, a key enzyme in leucine biosynthesis. Proc. Natl. Acad. Sci. U.S.A. 2004
Interaction	RegulatedBy Rv0757	yamir.moreno	IEP		Microarrays. mRNA levels of regulated element measured and compared between wild-type and trans-element mutation (knockout, over expression etc.) performed by using microarray (or macroarray) experiments.. SB. Walters, E. Dubnau et al. The Mycobacterium tuberculosis PhoPR two-component system regulates genes essential for virulence and complex lipid biosynthesis. Mol. Microbiol. 2006
Interaction	RegulatedBy Rv3291c	yamir.moreno	ISO		E.coli orthology based inference. Orthologous pair regulator-target found in E.coli. G. Balzsi, AP. Heath et al. The temporal response of the Mycobacterium tuberculosis gene regulatory network during growth arrest. Mol. Syst. Biol. 2008

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