LeuD

• Description: 3-isopropylmalate dehydratase (small subunit)
  
  

Gene name	leuD
Synonyms
Essential	no
Product	3-isopropylmalate dehydratase (small subunit)
Function	biosynthesis of leucine
Metabolic function and regulation of this protein in SubtiPathways: Ile, Leu, Val
MW, pI	22 kDa, 4.582
Gene length, protein length	597 bp, 199 aa
Immediate neighbours	ysoA, leuC
Get the DNA and protein sequences (Barbe et al., 2009)
Genetic context This image was kindly provided by SubtiList

The gene

Basic information

• Locus tag: BSU28250

Database entries

• 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: LeuD type 1 subfamily (according to Swiss-Prot)

• Paralogous protein(s):

Extended information on the protein

• Kinetic information:

• Domains:

• Modification:

• Cofactor(s): contains an iron-sulfur cluster

• Effectors of protein activity:

• Interactions:

• Localization:

Database entries

• Structure: 2PKP (from Methanocaldococcus jannaschii dsm 2661, 38% identity, 53% similarity)

• UniProt: P94568

• 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

• Sigma factor: SigA PubMed

• Regulation: for a complete overview on the regulation of the ilv operon, see Brinsmade et al.
  • repressed by casamino acids PubMed
  • expression is stimulated in the presence of glucose PubMed
  • 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

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

• Additional information: subject to Clp-dependent proteolysis upon glucose starvation PubMed

Biological materials

• Mutant:

• Expression vector:

• lacZ fusion:

• GFP fusion:

• two-hybrid system:

• Antibody:

References

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)

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)

Christine Eymann, Georg Homuth, Christian Scharf, Michael Hecker
Bacillus subtilis functional genomics: global characterization of the stringent response by proteome and transcriptome analysis.
J Bacteriol: 2002, 184(9);2500-20
[PubMed:11948165] [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)