TB Genome Annotation Portal

Rv3710 (leuA)

• Current annotations:
  • TBCAP: (community-based annotations - see table at bottom of page)
  • TBDB: 2-isopropylmalate synthase
  • REFSEQ: 2-isopropylmalate synthase
  • PATRIC: 2-isopropylmalate synthase (EC 2.3.3.13)
  • TUBERCULIST: 2-isopropylmalate synthase LeuA (alpha-isopropylmalate synthase) (alpha-IPM synthetase) (IPMS)
  • NCBI: 2-isopropylmalate synthase LeuA (alpha-isopropylmalate synthase) (alpha-IPM synthetase) (IPMS)
  • updated information (H37Rv4):
    • gene name: leuA
    • function:
    • reference:
• Type: Not Target
• Start: 4153740
• End: 4155674
• Operon:


• Trans-membrane region:
  
• Role: I.D.7 - Branched amino acid family
• GO terms:
  • GO:0046912 - transferase activity, transferring acyl groups, acyl groups converted into alkyl on transfer (Uniprot)
  • GO:0040007 - growth (Uniprot)
  • GO:0030955 - potassium ion binding (Uniprot)
  • GO:0030145 - manganese ion binding (Uniprot)
  • GO:0019752 - carboxylic acid metabolic process (Uniprot)
  • GO:0016740 - transferase activity (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:0008270 - zinc ion binding (Uniprot)
  • GO:0005886 - plasma membrane (Uniprot)
  • GO:0005576 - extracellular region (Uniprot)
  • GO:0005515 - protein binding (Uniprot)
  • GO:0003852 - 2-isopropylmalate synthase activity (Uniprot)
  • GO:0003824 - catalytic activity (Uniprot)
  • GO:0000287 - magnesium ion binding (Uniprot)
• Reaction(s) (based on iSM810 metabolic model):
  • ACCOA[c] + OMVAL[c] -> COA[c] + IPPMAL[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: 3fig, 3hps, 3hpz, 3hpx, 3hq1, 1sr9, 3u6w
• Search for Homologs in PDB
• Top 10 Homologs in PDB (as of Nov 2020):
  

  PDB	aa ident	species	PDB title
  3FIG	100%	Mycobacterium tuberculosis	Crystal Structure of Leucine-bound LeuA from Mycobacterium tuberculosis
  3HQ1	99%	Mycobacterium tuberculosis	Crystal structure of Mycobacterium tuberculosis LeuA complexed with citrate and Mn2+
  3HPZ	99%	Mycobacterium tuberculosis	Crystal structure of Mycobacterium tuberculosis LeuA complexed with bromopyruvate
  3HPS	99%	Mycobacterium tuberculosis	Crystal structure of Mycobacterium tuberculosis LeuA complexed with ketoisocaproate (KIC)
  1SR9	99%	Mycobacterium tuberculosis	Crystal Structure of LeuA from Mycobacterium tuberculosis
  3U6W	99%	Mycobacterium tuberculosis	Truncated M. tuberculosis LeuA (1-425) complexed with KIV
  3HPX	99%	Mycobacterium tuberculosis	Crystal structure of Mycobacterium tuberculosis LeuA active site domain 1-425 (truncation mutant delta:426-644)

• Links to additional information on leuA:
  • TBDB (updated)
  • Phyre2 structure prediction, model: final.casp.pdb (from Mao et al, 2013)
  • UniProt
  • AlphaFold model
  • Vulnerability = -1.147 (from Jeremy Rock's lab)
  • KEGG - nucleotide and amino acid sequences of gene
  • Mycobrowser
  • PATRIC
  • BioCyc
  • Systems Biology

Amino Acid Sequence

VTTSESPDAYTESFGAHTIVKPAGPPRVGQPSWNPQRASSMPVNRYRPFAEEVEPIRLRNRTWPDRVIDRAPLWCAVDLRDGNQALIDPMSPARKRRMFD
LLVRMGYKEIEVGFPSASQTDFDFVREIIEQGAIPDDVTIQVLTQCRPELIERTFQACSGAPRAIVHFYNSTSILQRRVVFRANRAEVQAIATDGARKCV
EQAAKYPGTQWRFEYSPESYTGTELEYAKQVCDAVGEVIAPTPERPIIFNLPATVEMTTPNVYADSIEWMSRNLANRESVILSLHPHNDRGTAVAAAELG
FAAGADRIEGCLFGNGERTGNVCLVTLGLNLFSRGVDPQIDFSNIDEIRRTVEYCNQLPVHERHPYGGDLVYTAFSGSHQDAINKGLDAMKLDADAADCD
VDDMLWQVPYLPIDPRDVGRTYEAVIRVNSQSGKGGVAYIMKTDHGLSLPRRLQIEFSQVIQKIAEGTAGEGGEVSPKEMWDAFAEEYLAPVRPLERIRQ
HVDAADDDGGTTSITATVKINGVETEISGSGNGPLAAFVHALADVGFDVAVLDYYEHAMSAGDDAQAAAYVEASVTIASPAQPGEAGRHASDPVTIASPA
QPGEAGRHASDPVTSKTVWGVGIAPSITTASLRAVVSAVNRAAR

Additional Information

Analysis of Positive Selection in Clinical Isolates *new*

• Analysis of dN/dS (omega) in two collections of Mtb clinical isolates using GenomegaMap (Window model) (see description of methods)
  • Moldova: 2,057 clinical isolates
  • global set: 5,195 clinical isolates from 15 other countries
• In the omega plots, the black line shows the mean estimate of omega (dN/dS) at each codon, and the blue lines are the bounds for the 95% credible interval (95%CI, from MCMC sampling).
• A gene is under significant positive selection if the lower-bound of the 95%CI of omega (lower blue line) exceeds 1.0 at any codon.

	Moldova (2,057)	global set (5,195)
under significant positive selection?	NO	NO
omega peak height (95%CI lower bound)	2.35 (0.58)	1.17 (0.54)
codons under selection
omega plots
genetic variants*	link	link
statistics at each codon	link	link