Gene Symbol: icd
Description: isocitrate dehydrogenase; e14 prophage attachment site; tellurite reductase
Alias: ECK1122, JW1122, icdA, icdE
Species: Escherichia coli str. K-12 substr. MG1655

Top Publications

  1. Song P, Li S, Wu Y, Lv C, Wang P, Zhu G. Point mutation (R153H or R153C) in Escherichia coli isocitrate dehydrogenase: Biochemical characterization and functional implication. J Basic Microbiol. 2017;57:41-49 pubmed publisher
    ..As human IDH1 Arg132 mutation is cancer-associated, the present study provides new information for the in-depth investigation of the metabolic influence of EcIDH Arg mutation in vivo. ..
  2. Borthwick A, Holms W, Nimmo H. The phosphorylation of Escherichia coli isocitrate dehydrogenase in intact cells. Biochem J. 1984;222:797-804 pubmed
    ..Only one phosphopeptide was observed in each case; the results show that the residue phosphorylated in vivo is identical with that phosphorylated by purified isocitrate dehydrogenase kinase in vitro. ..
  3. Wang F, Whittam T, Selander R. Evolutionary genetics of the isocitrate dehydrogenase gene (icd) in Escherichia coli and Salmonella enterica. J Bacteriol. 1997;179:6551-9 pubmed
    Sequences of the icd gene, encoding isocitrate dehydrogenase (IDH), were obtained for 33 strains representing the major phylogenetic lineages of Escherichia coli and Salmonella enterica...
  4. Stoddard B, Koshland D. Structure of isocitrate dehydrogenase with alpha-ketoglutarate at 2.7-A resolution: conformational changes induced by decarboxylation of isocitrate. Biochemistry. 1993;32:9317-22 pubmed
  5. Garnak M, Reeves H. Phosphorylation of Isocitrate dehydrogenase of Escherichia coli. Science. 1979;203:1111-2 pubmed
    ..This is the first example of protein phosphorylation in a bacterium in which the endogenous substrate for the protein kinase has been identified. ..
  6. Nimmo G, Nimmo H. The regulatory properties of isocitrate dehydrogenase kinase and isocitrate dehydrogenase phosphatase from Escherichia coli ML308 and the roles of these activities in the control of isocitrate dehydrogenase. Eur J Biochem. 1984;141:409-14 pubmed
    ..This theory can explain many recent observations on the control of the activity of isocitrate dehydrogenase. ..
  7. Reeves H, Daumy G, Lin C, Houston M. NADP + -specific isocitrate dehydrogenase of Escherichia coli. I. Purification and characterization. Biochim Biophys Acta. 1972;258:27-39 pubmed
  8. Choi I, Sup K, Kim H, Park J. Thermosensitive phenotype of Escherichia coli mutant lacking NADP+-dependent isocitrate dehydrogenase. Redox Rep. 2003;8:51-6 pubmed
    ..These results suggest that ICDH plays an important role as an antioxidant enzyme in cellular defense against heat shock through the removal of reactive oxygen species as well as in the protection of other antioxidant enzymes. ..
  9. Swim H, Krampitz L. Acetic acid oxidation by Escherichia coli; evidence for the occurrence of a tricarboxylic acid cycle. J Bacteriol. 1954;67:419-25 pubmed

More Information


  1. Lin H, Bennett G, San K. Genetic reconstruction of the aerobic central metabolism in Escherichia coli for the absolute aerobic production of succinate. Biotechnol Bioeng. 2005;89:148-56 pubmed
    ..Mutations in the tricarboxylic acid cycle (sdhAB, icd, iclR) and acetate pathways (poxB, ackA-pta) of E...
  2. Kalinina O, Gelfand M. Amino acid residues that determine functional specificity of NADP- and NAD-dependent isocitrate and isopropylmalate dehydrogenases. Proteins. 2006;64:1001-9 pubmed
    ..coli) that contact the cofactor and may play a role in the recognition process. ..
  3. Finer Moore J, Tsutakawa S, Cherbavaz D, LaPorte D, Koshland D, Stroud R. Access to phosphorylation in isocitrate dehydrogenase may occur by domain shifting. Biochemistry. 1997;36:13890-6 pubmed
  4. Hill C, Gray J, Brody H. Use of the isocitrate dehydrogenase structural gene for attachment of e14 in Escherichia coli K-12. J Bacteriol. 1989;171:4083-4 pubmed
    The e14 element appears to be integrated into the Escherichia coli K-12 isocitrate dehydrogenase structural gene (icd). In being integrated, it replaced the last 52 codons of the gene with a closely related sequence...
  5. Herold C, Birge E. Location of icdA and fadR on the physical map of Escherichia coli. J Bacteriol. 1990;172:6618 pubmed
  6. Helling R, Kukora J. Nalidixic acd-resistant mutants of Escherichia coli deficient in isocitrate dehydrogenase. J Bacteriol. 1971;105:1224-6 pubmed
    b>icd Mutants of Escherichia coli K-12, selected for their resistance to nalidixic acid, are deficient in isocitrate dehydrogenase.
  7. Batinic Haberle I, Benov L. An SOD mimic protects NADP+-dependent isocitrate dehydrogenase against oxidative inactivation. Free Radic Res. 2008;42:618-24 pubmed publisher
    ..b>ICD, however, is susceptible to oxidative inactivation, which in turn compromises cellular antioxidant defense...
  8. Jung I, Kim S, Kim I. The RpoS-mediated regulation of isocitrate dehydrogenase gene expression in Escherichia coli. Curr Microbiol. 2006;52:21-6 pubmed
    The Escherichia coli NADP(+)-dependent isocitrate dehydrogenase (IDH; EC, encoded by an icd gene, is a tricarboxylic acid (TCA) cycle enzyme responsible for the oxidative decarboxylation of isocitrate to alpha-ketoglutarate...
  9. Cozzone A, El Mansi M. Control of isocitrate dehydrogenase catalytic activity by protein phosphorylation in Escherichia coli. J Mol Microbiol Biotechnol. 2005;9:132-46 pubmed
    ..coli and related genera on acetate and fatty acids. ..
  10. Zhang J, Sprung R, Pei J, Tan X, Kim S, Zhu H, et al. Lysine acetylation is a highly abundant and evolutionarily conserved modification in Escherichia coli. Mol Cell Proteomics. 2009;8:215-25 pubmed publisher
    ..Furthermore, we demonstrate that bacterial lysine acetylation is regulated in response to stress stimuli. ..
  11. Dexter J, Gunawardena J. Dimerization and bifunctionality confer robustness to the isocitrate dehydrogenase regulatory system in Escherichia coli. J Biol Chem. 2013;288:5770-8 pubmed publisher
    ..Our work unifies much of the known biochemistry of the IDH regulatory system into a single quantitative framework and highlights the importance of constructing biochemically realistic models in systems biology...
  12. Wang H, Yang C, Lee G, Chang F, Wilson H, del Campillo Campbell A, et al. Integration specificities of two lambdoid phages (21 and e14) that insert at the same attB site. J Bacteriol. 1997;179:5705-11 pubmed
    It was shown previously that phage 21 and the defective element e14 integrate at the same site within the icd gene of Escherichia coli K-12 but that 21 integrase and excisionase excise e14 in vivo very infrequently compared to excision ..
  13. Lakshmi T, Helling R. Selection for citrate synthase deficiency in icd mutants of Escherichia coli. J Bacteriol. 1976;127:76-83 pubmed
    Cultures of isocitrate dehydrogenase-deficient (icd) mutants were overgrown by double mutants (icd glt) lacking citrate synthase activity also...
  14. Kabir M, Shimizu K. Metabolic regulation analysis of icd-gene knockout Escherichia coli based on 2D electrophoresis with MALDI-TOF mass spectrometry and enzyme activity measurements. Appl Microbiol Biotechnol. 2004;65:84-96 pubmed
    ..how the central metabolism of Escherichia coli changes upon knockout of the isocitrate dehydrogenase (ICDH) gene (icd) in the tricarboxylic acid cycle...
  15. Doyle S, Beernink P, Koshland D. Structural basis for a change in substrate specificity: crystal structure of S113E isocitrate dehydrogenase in a complex with isopropylmalate, Mg2+, and NADP. Biochemistry. 2001;40:4234-41 pubmed
    ..In combination, these interactions appear to provide the basis for the switch in substrate specificity. ..
  16. Murakami K, Tsubouchi R, Fukayama M, Ogawa T, Yoshino M. Oxidative inactivation of reduced NADP-generating enzymes in E. coli: iron-dependent inactivation with affinity cleavage of NADP-isocitrate dehydrogenase. Arch Microbiol. 2006;186:385-92 pubmed
    ..coli. ..
  17. Cherbavaz D, Lee M, Stroud R, Koshland D. Active site water molecules revealed in the 2.1 A resolution structure of a site-directed mutant of isocitrate dehydrogenase. J Mol Biol. 2000;295:377-85 pubmed
    ..Comparison of K230M complexed with isocitrate and alpha-ketoglutarate illuminates the influence a ligand has on active site water structure. ..
  18. Prost J, Negre D, Oudot C, Murakami K, Ishihama A, Cozzone A, et al. Cra-dependent transcriptional activation of the icd gene of Escherichia coli. J Bacteriol. 1999;181:893-8 pubmed
    The icd gene of Escherichia coli, encoding isocitrate dehydrogenase, was shown to be expressed from two different promoters: the previously identified icd P1 and a newly detected second promoter, icd P2, whose expression is positively ..
  19. Burke W, Swafford J, Reeves H. Crystallization of NADP-specific isocitrate dehydrogenase. Science. 1973;181:59-60 pubmed
    ..Scanning electron microscopy was employed to elucidate the structure of the crystals, which were found to exist as regular octahedrons ranging in size from 5 to 90 micrometers. ..
  20. Burke W, Johanson R, Reeves H. NADP+-specific isocitrate dehydrogenase of Escherichia coli. II. Subunit structure. Biochim Biophys Acta. 1974;351:333-40 pubmed
  21. Kohanski M, Dwyer D, Hayete B, Lawrence C, Collins J. A common mechanism of cellular death induced by bactericidal antibiotics. Cell. 2007;130:797-810 pubmed
    ..g., reca. ..
  22. Mesecar A, Stoddard B, Koshland D. Orbital steering in the catalytic power of enzymes: small structural changes with large catalytic consequences. Science. 1997;277:202-6 pubmed
    ..The results provide evidence that orbital overlap produced by optimal orientation of reacting orbitals plays a major quantitative role in the catalytic power of enzymes. ..
  23. Tsuchiya D, Shimizu N, Tomita M. Versatile architecture of a bacterial aconitase B and its catalytic performance in the sequential reaction coupled with isocitrate dehydrogenase. Biochim Biophys Acta. 2008;1784:1847-56 pubmed publisher
    ..Connecting the two proteins by a flexible linker yielded a locally high concentration to promote the weak protein-protein interaction. The versatile architecture of AcnB may alter the metabolic process involving the Krebs cycle. ..
  24. Hurley J, Chen R, Dean A. Determinants of cofactor specificity in isocitrate dehydrogenase: structure of an engineered NADP+ --> NAD+ specificity-reversal mutant. Biochemistry. 1996;35:5670-8 pubmed
    ..The side chain of this "second layer" residue dictates packing of the surrounding "first layer" residues which interact with the 2' moiety and, in turn, directly determine specificity. ..
  25. Hurley J, Dean A, Koshland D, Stroud R. Catalytic mechanism of NADP(+)-dependent isocitrate dehydrogenase: implications from the structures of magnesium-isocitrate and NADP+ complexes. Biochemistry. 1991;30:8671-8 pubmed
    ..E. coli isocitrate dehydrogenase transfers a hydride stereospecifically to the A-side of NADP+, and models for a reactive ternary complex consistent with this stereospecificity are discussed. ..
  26. Ogawa T, Murakami K, Mori H, Ishii N, Tomita M, Yoshin M. Role of phosphoenolpyruvate in the NADP-isocitrate dehydrogenase and isocitrate lyase reaction in Escherichia coli. J Bacteriol. 2007;189:1176-8 pubmed
  27. Zhang Z, Tan M, Xie Z, Dai L, Chen Y, Zhao Y. Identification of lysine succinylation as a new post-translational modification. Nat Chem Biol. 2011;7:58-63 pubmed publisher
    ..Given the apparent high abundance of lysine succinylation and the significant structural changes induced by this PTM, it is expected that lysine succinylation has important cellular functions. ..
  28. McKee J, Nimmo H. Evidence for an arginine residue at the coenzyme-binding site of Escherichia coli isocitrate dehydrogenase. Biochem J. 1989;261:301-4 pubmed
  29. Campbell A, Schneider S, Song B. Lambdoid phages as elements of bacterial genomes (integrase/phage21/Escherichia coli K-12/icd gene). Genetica. 1992;86:259-67 pubmed
    ..We suggest that this mode of insertion arose from insertion of an ancestral phage to the right of icd which then picked up part of the icd gene by abnormal excision and speculate that, at an earlier time, phages may ..
  30. Imabayashi F, Aich S, Prasad L, Delbaere L. Substrate-free structure of a monomeric NADP isocitrate dehydrogenase: an open conformation phylogenetic relationship of isocitrate dehydrogenase. Proteins. 2006;63:100-12 pubmed publisher
    ..This is done to examine evolutionary relationships...
  31. Walsh K, Koshland D. Branch point control by the phosphorylation state of isocitrate dehydrogenase. A quantitative examination of fluxes during a regulatory transition. J Biol Chem. 1985;260:8430-7 pubmed
    ..The modulation of protein phosphorylation and metabolite levels is one of the regulatory mechanisms which enables the bacterium to make dramatic shifts between metabolic pathways within a fraction of a doubling time. ..
  32. Lee M, Dyer D, Klein O, Bolduc J, Stoddard B, Koshland D. Mutational analysis of the catalytic residues lysine 230 and tyrosine 160 in the NADP(+)-dependent isocitrate dehydrogenase from Escherichia coli. Biochemistry. 1995;34:378-84 pubmed
    ..Hence, the alteration of the side chain functional groups is directly related to the loss of enzyme activity. Possible roles of the active site tyrosine and lysine are discussed. ..
  33. Bolduc J, Dyer D, Scott W, Singer P, Sweet R, Koshland D, et al. Mutagenesis and Laue structures of enzyme intermediates: isocitrate dehydrogenase. Science. 1995;268:1312-8 pubmed
    ..Mutation of key catalytic residues changed the rate determining steps so that protein and substrate intermediates within the overall reaction pathway could be visualized. ..
  34. Mesecar A, Koshland D. A new model for protein stereospecificity. Nature. 2000;403:614-5 pubmed
  35. Ranquet C, Ollagnier de Choudens S, Loiseau L, Barras F, Fontecave M. Cobalt stress in Escherichia coli. The effect on the iron-sulfur proteins. J Biol Chem. 2007;282:30442-51 pubmed
    ..We propose a model wherein cobalt competes out iron during synthesis of [Fe-S] clusters in metabolically essential proteins. ..
  36. Chen R, Grobler J, Hurley J, Dean A. Second-site suppression of regulatory phosphorylation in Escherichia coli isocitrate dehydrogenase. Protein Sci. 1996;5:287-95 pubmed
    ..These movements increase the distance between the carboxylates, diminish the electrostatic repulsion, and lead to the remarkably high activity of the S113E/N115L mutant. ..
  37. Dean A, Shiau A, Koshland D. Determinants of performance in the isocitrate dehydrogenase of Escherichia coli. Protein Sci. 1996;5:341-7 pubmed
    ..These results are entirely consistent with X-ray structures of Michaelis complexes that show a hydrogen bond positions the gamma-carboxylate of isocitrate so that a salt bridge can form to the nicotinamide ring of NADP. ..
  38. Hurley J, Dean A, Sohl J, Koshland D, Stroud R. Regulation of an enzyme by phosphorylation at the active site. Science. 1990;249:1012-6 pubmed
    ..Thus, direct interaction at a ligand binding site is an alternative mechanism to induced conformational changes from an allosteric site in the regulation of protein activity by phosphorylation. ..
  39. Aoshima M, Ishii M, Yamagishi A, Oshima T, Igarashi Y. Metabolic characteristics of an isocitrate dehydrogenase defective derivative of escherichia coli BL21(DE3). Biotechnol Bioeng. 2003;84:732-7 pubmed
    ..In addition, isocitrate lyase was not highly induced at the stationary phase. MA1935 was shown to be a good host strain for ICDH gene expression. ..
  40. Helling R, Janes B, Kimball H, Tran T, Bundesmann M, Check P, et al. Toxic waste disposal in Escherichia coli. J Bacteriol. 2002;184:3699-703 pubmed
    ..Nal(r)) mutants in a transposition-induced library exhibited a growth factor requirement as the result of cysH, icdA, metE, or purB mutation...
  41. Hurley J, Thorsness P, Ramalingam V, Helmers N, Koshland D, Stroud R. Structure of a bacterial enzyme regulated by phosphorylation, isocitrate dehydrogenase. Proc Natl Acad Sci U S A. 1989;86:8635-9 pubmed
    ..Based on the structure of isocitrate dehydrogenase and conservation with isopropylmalate dehydrogenase, we suggest that the active site lies in an interdomain pocket close to the phosphorylation site. ..
  42. Nimmo H. Kinetic mechanism of Escherichia coli isocitrate dehydrogenase and its inhibition by glyoxylate and oxaloacetate. Biochem J. 1986;234:317-23 pubmed
    ..The data suggest that the inhibition of isocitrate dehydrogenase by glyoxylate and oxaloacetate is not physiologically significant. ..
  43. Thorsness P, Koshland D. Inactivation of isocitrate dehydrogenase by phosphorylation is mediated by the negative charge of the phosphate. J Biol Chem. 1987;262:10422-5 pubmed
    ..To understand the mechanism by which phosphorylation inactivates isocitrate dehydrogenase, the sequence of icd, the isocitrate dehydrogenase structural gene, was determined and this information was used to construct mutants at ..
  44. Mesecar A, Koshland D. Sites of binding and orientation in a four-location model for protein stereospecificity. IUBMB Life. 2000;49:457-66 pubmed
    ..A four-location model is necessary to explain the enantiomeric specificity of IDH in contrast to the conventional three-point attachment model. The thermodynamic and kinetic ramifications of this model are explored. ..
  45. Doyle S, Fung S, Koshland D. Redesigning the substrate specificity of an enzyme: isocitrate dehydrogenase. Biochemistry. 2000;39:14348-55 pubmed
    ..Since interactions between neighboring residues in this region greatly influenced the effects of each other in unexpected ways, structural solutions were best identified in combinations, as allowed by random mutagenesis...
  46. Wright G. On the road to bacterial cell death. Cell. 2007;130:781-3 pubmed
    ..In this issue, Kohanski et al. (2007) provide evidence that the production of reactive oxygen species is a shared mechanism of cell death initiated by bactericidal antibiotics. ..
  47. LaPorte D, Walsh K, Koshland D. The branch point effect. Ultrasensitivity and subsensitivity to metabolic control. J Biol Chem. 1984;259:14068-75 pubmed
    ..5 decrease in the rate of isocitrate production. The mechanism which underlies this sensitivity amplification is discussed. ..
  48. Brody H, Greener A, Hill C. Excision and reintegration of the Escherichia coli K-12 chromosomal element e14. J Bacteriol. 1985;161:1112-7 pubmed
    ..We found the following sequence: fabD purB atte14 umuC. Furthermore, analysis of a recombinant plasmid that contained both the e14 attachment site and the purB locus showed that these two loci occur within 11 kilobases of each other. ..
  49. Chen R, Greer A, Dean A. A highly active decarboxylating dehydrogenase with rationally inverted coenzyme specificity. Proc Natl Acad Sci U S A. 1995;92:11666-70 pubmed
    ..Two additional mutations at remote sites improve performance further, resulting in a final mutant enzyme with kinetic characteristics and coenzyme preference comparable to naturally occurring homologous NAD-dependent enzymes. ..
  50. Greener A, Hill C. Identification of a novel genetic element in Escherichia coli K-12. J Bacteriol. 1980;144:312-21 pubmed
    ..In addition, e14 was found to be absent in both E. coli B/5 and E. coli C. The approach to mapping developed for this work could be used to map other fragments of E. coli deoxyribonucleic acid which have no known phenotype. ..