Gene - combatTB X

mbtI

Type: protein_coding
Name: mbtI
Locus Name: Rv2386c
Product: Isochorismate synthase MbtI
Functional Category: Lipid metabolism
Location: 2678653..2680005 (- strand)
Gene Length: 1352 bp
Nucleotides: GTGTCCGAGCTCAGCGTCGCGACAGGCGCCGTCAGCACCGCGTCGTCGTCCATCCCGATGCCCGCCGGTGTCAACCCCGCCGACCTGGCAGCGGAGCTGGCGGCGGTGGTTACCGAGTCCGTCGACGAGGATTACCTGCTCTACGAGTGCGACGGCCAATGGGTCCTGGCCGCCGGTGTGCAGGCGATGGTGGAGCTAGACAGCGACGAACTGCGCGTCATCCGTGATGGCGTTACGCGGCGACAGCAATGGTCGGGTCGCCCGGGAGCGGCCCTGGGCGAAGCCGTCGATCGGCTGTTGCTGGAAACCGATCAAGCTTTTGGCTGGGTCGCCTTCGAATTCGGCGTGCACCGCTATGGGTTGCAGCAGCGGCTGGCGCCGCACACCCCACTGGCCCGGGTGTTTTCGCCCCGAACCCGGATCATGGTGAGCGAAAAGGAGATTCGCCTGTTCGATGCTGGGATTCGCCACCGCGAGGCCATCGACCGATTACTCGCCACCGGGGTGCGAGAGGTGCCGCAGTCCCGCTCCGTCGACGTCTCCGACGATCCATCCGGCTTCCGCCGTCGGGTGGCGGTAGCCGTCGATGAAATCGCTGCCGGCCGCTACCACAAGGTGATTCTGTCCCGTTGTGTCGAAGTGCCTTTCGCGATCGACTTTCCGTTGACCTACCGGCTGGGGCGTCGGCACAACACCCCGGTGAGGTCGTTTTTGTTGCAGTTGGGCGGAATCCGTGCTCTGGGTTACAGCCCCGAACTCGTCACGGCGGTGCGCGCCGACGGAGTGGTGATCACCGAGCCGTTGGCCGGTACCCGCGCCTTGGGCCGTGGTCCCGCCATTGACCGACTGGCTCGTGATGACCTGGAATCAAACTCCAAAGAAATTGTCGAGCACGCCATTTCAGTGCGCTCTTCGCTTGAGGAGATTACCGACATCGCCGAACCAGGGAGTGCTGCGGTCATCGATTTCATGACGGTGCGCGAGCGCGGCAGTGTGCAGCACCTCGGCTCCACCATCAGAGCACGGTTGGATCCATCGAGCGACCGGATGGCCGCCCTGGAAGCCCTTTTTCCTGCTGTCACTGCATCCGGAATCCCGAAAGCAGCTGGCGTTGAGGCCATCTTTCGCCTCGATGAGTGCCCACGTGGGCTGTATTCCGGTGCGGTGGTGATGCTTTCGGCGGATGGCGGGCTAGACGCCGCGCTGACGCTGCGGGCGGCATACCAGGTCGGCGGGCGGACTTGGCTGCGGGCCGGCGCCGGCATCATCGAAGAATCGGAGCCAGAGCGCGAATTCGAGGAGACTTGCGAAAAGCTATCCACATTGACGCCTTATCTGGTTGCACGCCAGTA
Drug Resistance: Check for drug resistance association at TBDREAMDB
Mutations: Check for mutants available at TARGET

Function

Involved in the incorporation of salicylate into the virulence-conferring salicylate-based siderophore mycobactin. Catalyzes the initial conversion of chorismate to yield the intermediate isochorismate (isochorismate synthase activity), and the subsequent elimination of the enolpyruvyl side chain to give salicylate (isochorismate pyruvate-lyase activity). In the absence of magnesium, MbtI displays a chorismate mutase activity and converts chorismate to prephenate. {ECO:0000269|PubMed:16923875, ECO:0000269|PubMed:17240979, ECO:0000269|PubMed:20487026, ECO:0000269|PubMed:20512795, ECO:0000269|PubMed:9831524}.

Family

Anthranilate synthase component I family, Salicylate synthase subfamily

GO

chorismate mutase activity GO:0004106 molecular_function
isochorismate pyruvate lyase activity GO:0043904 molecular_function
oxo-acid-lyase activity GO:0016833 molecular_function
plasma membrane GO:0005886 cellular_component
isochorismate synthase activity GO:0008909 molecular_function
response to host immune response GO:0052572 biological_process
magnesium ion binding GO:0000287 molecular_function
cellular response to iron ion starvation GO:0010106 biological_process
salicylic acid biosynthetic process GO:0009697 biological_process
siderophore biosynthetic process from catechol GO:0019540 biological_process

InterPro

UniProt: P9WFX1
GenBank: Rv2386c
EnsemblBacteria: Rv2386c
Mycobrowser: Rv2386c

PDB IDs:

Summary

Name: Salicylate synthase (Chorismate mutase) (CM) (EC 5.4.99.5) (Isochorismate synthase/isochorismate lyase) (EC 4.2.99.21) (EC 5.4.4.2) (Mycobactin synthase protein)
Family: Anthranilate synthase component I family, Salicylate synthase subfamily
Protein Sequence: MSELSVATGAVSTASSSIPMPAGVNPADLAAELAAVVTESVDEDYLLYECDGQWVLAAGVQAMVELDSDELRVIRDGVTRRQQWSGRPGAALGEAVDRLLLETDQAFGWVAFEFGVHRYGLQQRLAPHTPLARVFSPRTRIMVSEKEIRLFDAGIRHREAIDRLLATGVREVPQSRSVDVSDDPSGFRRRVAVAVDEIAAGRYHKVILSRCVEVPFAIDFPLTYRLGRRHNTPVRSFLLQLGGIRALGYSPELVTAVRADGVVITEPLAGTRALGRGPAIDRLARDDLESNSKEIVEHAISVRSSLEEITDIAEPGSAAVIDFMTVRERGSVQHLGSTIRARLDPSSDRMAALEALFPAVTASGIPKAAGVEAIFRLDECPRGLYSGAVVMLSADGGLDAALTLRAAYQVGGRTWLRAGAGIIEESEPEREFEETCEKLSTLTPYLVARQ
Mass: 48,754 Da
Length: 450 Aa

Rv2386c doesn't seem to be a targeted by any drug.

Rv2386c doesn't seem to be involved in any pathway.

Implications of binding mode and active site flexibility for inhibitor potency against the salicylate synthase from Mycobacterium tuberculosis.: Biochemistry. 2012 Jun 19;51(24):4868-79. doi: 10.1021/bi3002067. Epub 2012 Jun 7.
Inhibition studies of Mycobacterium tuberculosis salicylate synthase (MbtI).: ChemMedChem. 2010 Jul 5;5(7):1067-79. doi: 10.1002/cmdc.201000137.
Structure and mechanism of MbtI, the salicylate synthase from Mycobacterium tuberculosis.: Biochemistry. 2007 Jan 30;46(4):954-64. doi: 10.1021/bi060852x.
The structure of MbtI from Mycobacterium tuberculosis, the first enzyme in the biosynthesis of the siderophore mycobactin, reveals it to be a salicylate synthase.: J Bacteriol. 2006 Sep;188(17):6081-91. doi: 10.1128/JB.00338-06.
Proteogenomic analysis of Mycobacterium tuberculosis by high resolution mass spectrometry.: Mol Cell Proteomics. 2011 Dec;10(12):M111.011627. doi: 10.1074/mcp.M111.011445. Epub 2011 Oct 3.
Roles of trpE2, entC and entD in salicylic acid biosynthesis in Mycobacterium smegmatis.: FEMS Microbiol Lett. 2010 Jul;308(2):159-65. doi: 10.1111/j.1574-6968.2010.02004.x. Epub 2010 Apr 28.
Crystallization and preliminary X-ray crystallographic analysis of MbtI, a protein essential for siderophore biosynthesis in Mycobacterium tuberculosis.: Acta Crystallogr Sect F Struct Biol Cryst Commun. 2005 Jan 1;61(Pt 1):121-3. doi: 10.1107/S1744309104031215. Epub 2004 Dec 24.
The Mycobacterium tuberculosis IdeR is a dual functional regulator that controls transcription of genes involved in iron acquisition, iron storage and survival in macrophages.: Mol Microbiol. 2001 Nov;42(3):851-65.
Identification of a Mycobacterium tuberculosis gene cluster encoding the biosynthetic enzymes for assembly of the virulence-conferring siderophore mycobactin.: Chem Biol. 1998 Nov;5(11):631-45.
Deciphering the biology of Mycobacterium tuberculosis from the complete genome sequence.: Nature. 1998 Jun 11;393(6685):537-44. doi: 10.1038/31159.