LeuC

• Description: 3-isopropylmalate dehydratase (large subunit)
  
  

Gene name	leuC
Synonyms
Essential	no
Product	3-isopropylmalate dehydratase (large subunit)
Function	biosynthesis of leucine
Gene expression levels in SubtiExpress: leuC
Metabolic function and regulation of this protein in SubtiPathways: leuC
MW, pI	52 kDa, 6.127
Gene length, protein length	1416 bp, 472 aa
Immediate neighbours	leuD, leuB
Sequences	Protein DNA DNA_with_flanks
Genetic context This image was kindly provided by SubtiList
Expression at a glance   PubMed

Categories containing this gene/protein

biosynthesis/ acquisition of amino acids, phosphoproteins, most abundant proteins

This gene is a member of the following regulons

CcpA regulon, CodY regulon, FsrA regulon, T-box, TnrA regulon

The gene

Basic information

• Locus tag: BSU28260

Database entries

• BsubCyc: BSU28260

• DBTBS entry: [1]

• SubtiList entry: [2]

The protein

Basic information/ Evolution

• Catalyzed reaction/ biological activity: (2R,3S)-3-isopropylmalate = (2S)-2-isopropylmaleate + H₂O (according to Swiss-Prot)

• Protein family: LeuC type 1 subfamily (according to Swiss-Prot)

• Paralogous protein(s):

Extended information on the protein

• Kinetic information:

• Domains:

• Modification:
  • phosphorylated on Arg-81 PubMed

• Cofactors: contains an iron-sulfur cluster

• Effectors of protein activity:

• Interactions:

• Localization:

Database entries

• BsubCyc: BSU28260

• Structure:

• UniProt: P80858

• KEGG entry: [3]

• E.C. number: 4.2.1.33

Additional information

• subject to Clp-dependent proteolysis upon glucose starvation PubMed

Expression and regulation

• Operon: ilvB-ilvH-ilvC-leuA-leuB-leuC-leuD PubMed

• Expression browser: leuC PubMed

• Sigma factor: SigA PubMed

• Regulation:
  • for a complete overview on the regulation of the ilv operon, see Brinsmade et al.
  • repressed in the absence of good nitrogen sources (glutamine or ammonium) (TnrA) PubMed
  • repressed during growth in the presence of branched chain amino acids (CodY) PubMed
  • repressed by casamino acids PubMed
  • expression is stimulated in the presence of glucose PubMed
  • less expressed under conditions of extreme iron limitation (FsrA) PubMed

• Regulatory mechanism:
  • TnrA: transcription repression PubMed
  • CodY: transcription repression PubMed
  • glucose regulation: CcpA PubMed
  • repression by BCAA: tRNA-controlled RNA switch (T-box) that mediates termination/antitermination
  • FsrA: translational repression PubMed

• Additional information:
  • subject to Clp-dependent proteolysis upon glucose starvation PubMed
  • belongs to the 100 most abundant proteins PubMed
  • number of protein molecules per cell (minimal medium with glucose and ammonium): 751 PubMed
  • number of protein molecules per cell (complex medium with amino acids, without glucose): 360 PubMed
  • number of protein molecules per cell (minimal medium with glucose and ammonium, exponential phase): 1636 PubMed
  • number of protein molecules per cell (minimal medium with glucose and ammonium, early stationary phase after glucose exhaustion): 1150 PubMed
  • number of protein molecules per cell (minimal medium with glucose and ammonium, late stationary phase after glucose exhaustion): 741 PubMed

Biological materials

• Mutant:

• Expression vector:

• lacZ fusion:

• GFP fusion:

• two-hybrid system:

• Antibody:

References

Yasutaro Fujita, Takenori Satomura, Shigeo Tojo, Kazutake Hirooka
CcpA-mediated catabolite activation of the Bacillus subtilis ilv-leu operon and its negation by either CodY- or TnrA-mediated negative regulation.
J Bacteriol: 2014, 196(21);3793-806
[PubMed:25157083] [WorldCat.org] [DOI] (I p)

Allison Kriel, Shaun R Brinsmade, Jessica L Tse, Ashley K Tehranchi, Alycia N Bittner, Abraham L Sonenshein, Jue D Wang
GTP dysregulation in Bacillus subtilis cells lacking (p)ppGpp results in phenotypic amino acid auxotrophy and failure to adapt to nutrient downshift and regulate biosynthesis genes.
J Bacteriol: 2014, 196(1);189-201
[PubMed:24163341] [WorldCat.org] [DOI] (I p)

Alexander K W Elsholz, Kürsad Turgay, Stephan Michalik, Bernd Hessling, Katrin Gronau, Dan Oertel, Ulrike Mäder, Jörg Bernhardt, Dörte Becher, Michael Hecker, Ulf Gerth
Global impact of protein arginine phosphorylation on the physiology of Bacillus subtilis.
Proc Natl Acad Sci U S A: 2012, 109(19);7451-6
[PubMed:22517742] [WorldCat.org] [DOI] (I p)

Shaun R Brinsmade, Roelco J Kleijn, Uwe Sauer, Abraham L Sonenshein
Regulation of CodY activity through modulation of intracellular branched-chain amino acid pools.
J Bacteriol: 2010, 192(24);6357-68
[PubMed:20935095] [WorldCat.org] [DOI] (I p)

Ana Gutiérrez-Preciado, Tina M Henkin, Frank J Grundy, Charles Yanofsky, Enrique Merino
Biochemical features and functional implications of the RNA-based T-box regulatory mechanism.
Microbiol Mol Biol Rev: 2009, 73(1);36-61
[PubMed:19258532] [WorldCat.org] [DOI] (I p)

Ahmed Gaballa, Haike Antelmann, Claudio Aguilar, Sukhjit K Khakh, Kyung-Bok Song, Gregory T Smaldone, John D Helmann
The Bacillus subtilis iron-sparing response is mediated by a Fur-regulated small RNA and three small, basic proteins.
Proc Natl Acad Sci U S A: 2008, 105(33);11927-32
[PubMed:18697947] [WorldCat.org] [DOI] (I p)

Shigeo Tojo, Takenori Satomura, Kanako Kumamoto, Kazutake Hirooka, Yasutaro Fujita
Molecular mechanisms underlying the positive stringent response of the Bacillus subtilis ilv-leu operon, involved in the biosynthesis of branched-chain amino acids.
J Bacteriol: 2008, 190(18);6134-47
[PubMed:18641142] [WorldCat.org] [DOI] (I p)

Shigeo Tojo, Takenori Satomura, Kaori Morisaki, Ken-Ichi Yoshida, Kazutake Hirooka, Yasutaro Fujita
Negative transcriptional regulation of the ilv-leu operon for biosynthesis of branched-chain amino acids through the Bacillus subtilis global regulator TnrA.
J Bacteriol: 2004, 186(23);7971-9
[PubMed:15547269] [WorldCat.org] [DOI] (P p)

Christine Eymann, Annette Dreisbach, Dirk Albrecht, Jörg Bernhardt, Dörte Becher, Sandy Gentner, Le Thi Tam, Knut Büttner, Gerrit Buurman, Christian Scharf, Simone Venz, Uwe Völker, Michael Hecker
A comprehensive proteome map of growing Bacillus subtilis cells.
Proteomics: 2004, 4(10);2849-76
[PubMed:15378759] [WorldCat.org] [DOI] (P p)

Ulrike Mäder, Susanne Hennig, Michael Hecker, Georg Homuth
Transcriptional organization and posttranscriptional regulation of the Bacillus subtilis branched-chain amino acid biosynthesis genes.
J Bacteriol: 2004, 186(8);2240-52
[PubMed:15060025] [WorldCat.org] [DOI] (P p)

Virginie Molle, Yoshiko Nakaura, Robert P Shivers, Hirotake Yamaguchi, Richard Losick, Yasutaro Fujita, Abraham L Sonenshein
Additional targets of the Bacillus subtilis global regulator CodY identified by chromatin immunoprecipitation and genome-wide transcript analysis.
J Bacteriol: 2003, 185(6);1911-22
[PubMed:12618455] [WorldCat.org] [DOI] (P p)

Holger Ludwig, Christoph Meinken, Anastasija Matin, Jörg Stülke
Insufficient expression of the ilv-leu operon encoding enzymes of branched-chain amino acid biosynthesis limits growth of a Bacillus subtilis ccpA mutant.
J Bacteriol: 2002, 184(18);5174-8
[PubMed:12193635] [WorldCat.org] [DOI] (P p)

Ulrike Mäder, Georg Homuth, Christian Scharf, Knut Büttner, Rüdiger Bode, Michael Hecker
Transcriptome and proteome analysis of Bacillus subtilis gene expression modulated by amino acid availability.
J Bacteriol: 2002, 184(15);4288-95
[PubMed:12107147] [WorldCat.org] [DOI] (P p)

F J Grundy, T M Henkin
Conservation of a transcription antitermination mechanism in aminoacyl-tRNA synthetase and amino acid biosynthesis genes in gram-positive bacteria.
J Mol Biol: 1994, 235(2);798-804
[PubMed:8289305] [WorldCat.org] [DOI] (P p)