TB Genome Annotation Portal

Rv2386c (mbtI)

• Current annotations:
  • TBCAP: (community-based annotations - see table at bottom of page)
  • TBDB: isochorismate synthase/isochorismate-pyruvate lyase mbtI
  • REFSEQ: salicylate synthase MbtI
  • PATRIC: isochorismate synthase MbtI
  • TUBERCULIST: Isochorismate synthase MbtI
  • NCBI: Isochorismate synthase MbtI
  • updated information (H37Rv4):
    • gene name: mbtI
    • function:
    • reference:
• Type: Not Target
• Start: 2678653
• End: 2680005
• Operon:


• Trans-membrane region:
  
• Role: I.D.4 - Aromatic amino acid family
• GO terms:
  • GO:0052572 - response to host immune response (Uniprot)
  • GO:0046872 - metal ion binding (Uniprot)
  • GO:0043904 - isochorismate pyruvate lyase activity (Uniprot)
  • GO:0040007 - growth (Uniprot)
  • GO:0019540 - siderophore biosynthetic process from catechol (Uniprot)
  • GO:0016853 - isomerase activity (Uniprot)
  • GO:0016833 - oxo-acid-lyase activity (Uniprot)
  • GO:0016829 - lyase activity (Uniprot)
  • GO:0010106 - cellular response to iron ion starvation (Uniprot)
  • GO:0009697 - salicylic acid biosynthetic process (Uniprot)
  • GO:0009058 - biosynthetic process (Uniprot)
  • GO:0008909 - isochorismate synthase activity (Uniprot)
  • GO:0005950 - anthranilate synthase complex (Uniprot)
  • GO:0005886 - plasma membrane (Uniprot)
  • GO:0004106 - chorismate mutase activity (Uniprot)
  • GO:0004049 - anthranilate synthase activity (Uniprot)
  • GO:0000287 - magnesium ion binding (Uniprot)
  • GO:0000162 - tryptophan biosynthetic process (Uniprot)
• Reaction(s) (based on iSM810 metabolic model):
  • CHOR[c] <=> ICHOR[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: 3log, 2i6y, 3rv8, 3rv9, 3rv6, 3rv7, 3veh, 3log, 2g5f, 3st6
• Search for Homologs in PDB
• Top 10 Homologs in PDB (as of Nov 2020):
  

  PDB	aa ident	species	PDB title
  3RV9	100%	Mycobacterium tuberculosis	Structure of a M. tuberculosis Salicylate Synthase, MbtI, in Complex with an Inhibitor with Ethyl R-Group
  3RV7	100%	Mycobacterium tuberculosis	Structure of a M. tuberculosis Salicylate Synthase, MbtI, in Complex with an Inhibitor with Isopropyl R-Group
  3RV6	100%	Mycobacterium tuberculosis	Structure of a M. tuberculosis Salicylate Synthase, MbtI, in Complex with an Inhibitor with Phenyl R-Group
  2I6Y	100%	Mycobacterium tuberculosis	Structure and Mechanism of Mycobacterium tuberculosis Salicylate Synthase, MbtI
  2G5F	100%	Mycobacterium tuberculosis	The structure of MbtI from Mycobacterium Tuberculosis, the first enzyme in the synthesis of Mycobactin, reveals it to be a salicylate synthase
  6ZA6	99%	Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)	M. tuberculosis salicylate synthase MbtI in complex with Ba2+
  6ZA5	99%	Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)	M. tuberculosis salicylate synthase MbtI in complex with salicylate and Mg2+
  6ZA4	99%	Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)	M. tuberculosis salicylate synthase MbtI in complex with 5-(3-cyanophenyl)furan-2-carboxylate
  3VEH	99%	Mycobacterium tuberculosis	Structure of a M. tuberculosis salicylate synthase, MbtI, in complex with an inhibitor methylAMT
  3ST6	99%	Mycobacterium tuberculosis	Structure of a M. tuberculosis Synthase, MbtI, in Complex with an Isochorismate Analogue Inhibitor

• Links to additional information on mbtI:
  • 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 = -0.423 (from Jeremy Rock's lab)

Amino Acid Sequence

VSELSVATGAVSTASSSIPMPAGVNPADLAAELAAVVTESVDEDYLLYECDGQWVLAAGVQAMVELDSDELRVIRDGVTRRQQWSGRPGAALGEAVDRLL
LETDQAFGWVAFEFGVHRYGLQQRLAPHTPLARVFSPRTRIMVSEKEIRLFDAGIRHREAIDRLLATGVREVPQSRSVDVSDDPSGFRRRVAVAVDEIAA
GRYHKVILSRCVEVPFAIDFPLTYRLGRRHNTPVRSFLLQLGGIRALGYSPELVTAVRADGVVITEPLAGTRALGRGPAIDRLARDDLESNSKEIVEHAI
SVRSSLEEITDIAEPGSAAVIDFMTVRERGSVQHLGSTIRARLDPSSDRMAALEALFPAVTASGIPKAAGVEAIFRLDECPRGLYSGAVVMLSADGGLDA
ALTLRAAYQVGGRTWLRAGAGIIEESEPEREFEETCEKLSTLTPYLVARQ

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)	1.57 (0.19)	0.97 (0.32)
codons under selection
omega plots
genetic variants*	link	link
statistics at each codon	link	link