Icd

• Description: isocitrate dehydrogenase
  
  

Gene name	icd
Synonyms	citC
Essential	no
Product	isocitrate dehydrogenase
Function	TCA cycle
Gene expression levels in SubtiExpress: icd
Interactions involving this protein in SubtInteract: Icd
Metabolic function and regulation of this protein in SubtiPathways: icd
MW, pI	46 kDa, 4.833
Gene length, protein length	1269 bp, 423 aa
Immediate neighbours	mdh, citZ
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

carbon core metabolism, membrane proteins, phosphoproteins, most abundant proteins

This gene is a member of the following regulons

CcpA regulon, CcpC regulon

The gene

Basic information

• Locus tag: BSU29130

Phenotypes of a mutant

• • reduced ability to sporulate PubMed
  • growth and sporulation defects of the mutant could be partially bypassed by deletion of the major citrate synthase gene (citZ) PubMed

Database entries

• BsubCyc: BSU29130

• DBTBS entry: [1]

• SubtiList entry: [2]

The protein

Basic information/ Evolution

• Catalyzed reaction/ biological activity: Isocitrate + NADP⁺ = 2-oxoglutarate + CO₂ + NADPH (according to Swiss-Prot)

• Protein family: isocitrate and isopropylmalate dehydrogenases family (according to Swiss-Prot)

• Paralogous protein(s):

Extended information on the protein

• Kinetic information:
  • Reversible Michaelis-Menten PubMed
  • specific activity: 1.64 µmol min^-1 (mg protein)^-1 PubMed

• Domains:

• Modification:
  • phosphorylated on Arg-180 PubMed
  • phosphorylated PubMed, PubMed
  • in vitro phosphorylated by PrkC on Thr-138, Thr-147, and Thr-396 PubMed

• Cofactors: Mg²⁺, Mn²⁺, NADP⁺

• Effectors of protein activity:
  • Inhibited by glyoxylate, oxaloacetate and oxalomalate PubMed
    • Better inhibition when glyoxylate and oxaloacetate is combined, probably due to the non-enzymatic conversion into oxalomalate, which is a strong inhibitor PubMed

• Interactions:
  • homodimer PubMed
  • CitZ-Mdh-Icd (this is the core of the TCA cycle metabolon) PubMed
  • Mdh-Icd PubMed
  • GltA-Icd PubMed
  • OdhB-Icd PubMed

• Localization: attached to the membrane PubMed

Database entries

• BsubCyc: BSU29130

• Structure: 1HQS

• UniProt: P39126

• KEGG entry: [3]

• E.C. number: 1.1.1.42

Additional information

• This enzyme requires NADP+ exclusively. No activity was seen on the presence on NAD+ PubMed
• extensive information on the structure and enzymatic properties of Icd can be found at Proteopedia

Expression and regulation

• Operon:
  • citZ-icd-mdh PubMed
  • icd-mdh PubMed

• Expression browser: icd PubMed

• Sigma factor:
  • citZ: SigA PubMed
  • icd: SigA PubMed

• Regulation:
  • citZ: catabolite repression (CcpA) PubMed
  • citZ: repression by glucose + glutamate (CcpC) PubMed

• Regulatory mechanism:
  • CcpA: transcription repression, CcpC: transcription repression PubMed
  • CcpC: transcription repression (molecular inducer: citrate) PubMed

• Additional information:
  • belongs to the 100 most abundant proteins PubMed
  • number of protein molecules per cell (minimal medium with glucose and ammonium): 37100 PubMed
  • number of protein molecules per cell (complex medium with amino acids, without glucose): 77080 PubMed
  • number of protein molecules per cell (minimal medium with glucose and ammonium, exponential phase): 41324 PubMed
  • number of protein molecules per cell (minimal medium with glucose and ammonium, early stationary phase after glucose exhaustion): 16631 PubMed
  • number of protein molecules per cell (minimal medium with glucose and ammonium, late stationary phase after glucose exhaustion): 32135 PubMed

Biological materials

• Mutant: GP666 (spc), GP672 (erm), available in Jörg Stülke's lab
  • 1A1000 ( icd::spec), PubMed, available at BGSC
  • 1A999 ( icd::spec), PubMed, available at BGSC
  • GP790 (citZ-icd-mdh::kan), available in Jörg Stülke's lab

• Expression vector:
  • pGP1121 (N-terminal Strep-tag, for SPINE, purification from B. subtilis, in pGP380) (available in Jörg Stülke's lab)

• lacZ fusion:

• GFP fusion:

• two-hybrid system: B. pertussis adenylate cyclase-based bacterial two hybrid system (BACTH), available in Jörg Stülke's lab

• Antibody: available in Linc Sonenshein's lab

Labs working on this gene/protein

Linc Sonenshein, Tufts University, Boston, MA, USA Homepage

References

Uppu Venkateswara Prasad, Vimjam Swarupa, Sthanikam Yeswanth, Pasupuleti Santhosh Kumar, Easambadi Siva Kumar, Kalikiri Mahesh Kumar Reddy, Yellapu Nanda Kumar, Vangavaragu Jhansi Rani, Abhijit Chaudhary, Potukuchi Venkata Gurunadha Krishna Sarma
Structural and Functional analysis of Staphylococcus aureus NADP-dependent IDH and its comparison with Bacterial and Human NADPdependent IDH.
Bioinformation: 2014, 10(2);81-6
[PubMed:24616559] [WorldCat.org] [DOI] (P e)

Michael Kohlstedt, Praveen K Sappa, Hanna Meyer, Sandra Maaß, Adrienne Zaprasis, Tamara Hoffmann, Judith Becker, Leif Steil, Michael Hecker, Jan Maarten van Dijl, Michael Lalk, Ulrike Mäder, Jörg Stülke, Erhard Bremer, Uwe Völker, Christoph Wittmann
Adaptation of Bacillus subtilis carbon core metabolism to simultaneous nutrient limitation and osmotic challenge: a multi-omics perspective.
Environ Microbiol: 2014, 16(6);1898-917
[PubMed:24571712] [WorldCat.org] [DOI] (I p)

Maike Bartholomae, Frederik M Meyer, Fabian M Commichau, Andreas Burkovski, Wolfgang Hillen, Gerald Seidel
Complex formation between malate dehydrogenase and isocitrate dehydrogenase from Bacillus subtilis is regulated by tricarboxylic acid cycle metabolites.
FEBS J: 2014, 281(4);1132-43
[PubMed:24325460] [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)

Frederik M Meyer, Jan Gerwig, Elke Hammer, Christina Herzberg, Fabian M Commichau, Uwe Völker, Jörg Stülke
Physical interactions between tricarboxylic acid cycle enzymes in Bacillus subtilis: evidence for a metabolon.
Metab Eng: 2011, 13(1);18-27
[PubMed:20933603] [WorldCat.org] [DOI] (I p)

Nico Pietack, Dörte Becher, Sebastian R Schmidl, Milton H Saier, Michael Hecker, Fabian M Commichau, Jörg Stülke
In vitro phosphorylation of key metabolic enzymes from Bacillus subtilis: PrkC phosphorylates enzymes from different branches of basic metabolism.
J Mol Microbiol Biotechnol: 2010, 18(3);129-40
[PubMed:20389117] [WorldCat.org] [DOI] (I p)

Hannes Hahne, Susanne Wolff, Michael Hecker, Dörte Becher
From complementarity to comprehensiveness--targeting the membrane proteome of growing Bacillus subtilis by divergent approaches.
Proteomics: 2008, 8(19);4123-36
[PubMed:18763711] [WorldCat.org] [DOI] (I p)

Christine Eymann, Dörte Becher, Jörg Bernhardt, Katrin Gronau, Anja Klutzny, Michael Hecker
Dynamics of protein phosphorylation on Ser/Thr/Tyr in Bacillus subtilis.
Proteomics: 2007, 7(19);3509-26
[PubMed:17726680] [WorldCat.org] [DOI] (P p)

Alain Lévine, Françoise Vannier, Cédric Absalon, Lauriane Kuhn, Peter Jackson, Elaine Scrivener, Valérie Labas, Joëlle Vinh, Patrick Courtney, Jérôme Garin, Simone J Séror
Analysis of the dynamic Bacillus subtilis Ser/Thr/Tyr phosphoproteome implicated in a wide variety of cellular processes.
Proteomics: 2006, 6(7);2157-73
[PubMed:16493705] [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)

Hans-Matti Blencke, Georg Homuth, Holger Ludwig, Ulrike Mäder, Michael Hecker, Jörg Stülke
Transcriptional profiling of gene expression in response to glucose in Bacillus subtilis: regulation of the central metabolic pathways.
Metab Eng: 2003, 5(2);133-49
[PubMed:12850135] [WorldCat.org] [DOI] (P p)

Satinder K Singh, Stephen P Miller, Antony Dean, Leonard J Banaszak, David C LaPorte
Bacillus subtilis isocitrate dehydrogenase. A substrate analogue for Escherichia coli isocitrate dehydrogenase kinase/phosphatase.
J Biol Chem: 2002, 277(9);7567-73
[PubMed:11751849] [WorldCat.org] [DOI] (P p)

S K Singh, K Matsuno, D C LaPorte, L J Banaszak
Crystal structure of Bacillus subtilis isocitrate dehydrogenase at 1.55 A. Insights into the nature of substrate specificity exhibited by Escherichia coli isocitrate dehydrogenase kinase/phosphatase.
J Biol Chem: 2001, 276(28);26154-63
[PubMed:11290745] [WorldCat.org] [DOI] (P p)

C Jourlin-Castelli, N Mani, M M Nakano, A L Sonenshein
CcpC, a novel regulator of the LysR family required for glucose repression of the citB gene in Bacillus subtilis.
J Mol Biol: 2000, 295(4);865-78
[PubMed:10656796] [WorldCat.org] [DOI] (P p)

K Matsuno, T Blais, A W Serio, T Conway, T M Henkin, A L Sonenshein
Metabolic imbalance and sporulation in an isocitrate dehydrogenase mutant of Bacillus subtilis.
J Bacteriol: 1999, 181(11);3382-91
[PubMed:10348849] [WorldCat.org] [DOI] (P p)

S Jin, P A Levin, K Matsuno, A D Grossman, A L Sonenshein
Deletion of the Bacillus subtilis isocitrate dehydrogenase gene causes a block at stage I of sporulation.
J Bacteriol: 1997, 179(15);4725-32
[PubMed:9244258] [WorldCat.org] [DOI] (P p)

R F Ramaley, M O Hudock
Purification and properties of isocitrate dehydrogenase (NADP) from Thermus aquaticus YT-1, Bacillus subtilis-168 and Chlamydomonas reinhardti-Y-2.
Biochim Biophys Acta: 1973, 315(1);22-36
[PubMed:4147570] [WorldCat.org] [DOI] (P p)