Gene Symbol: aceK
Description: isocitrate dehydrogenase kinase/phosphatase
Alias: ECK4008, JW3976
Species: Escherichia coli str. K-12 substr. MG1655
Products:     aceK

Top Publications

  1. Miller S, Karschnia E, Ikeda T, LaPorte D. Isocitrate dehydrogenase kinase/phosphatase. Kinetic characteristics of the wild-type and two mutant proteins. J Biol Chem. 1996;271:19124-8 pubmed
    ..The intrinsic ATPase activities also exhibited reduced affinity for ATP. These results are discussed in the context of a model which proposes that all three activities occur at the same active site. ..
  2. LaPorte D, Koshland D. A protein with kinase and phosphatase activities involved in regulation of tricarboxylic acid cycle. Nature. 1982;300:458-60 pubmed
  3. LaPorte D, Thorsness P, Koshland D. Compensatory phosphorylation of isocitrate dehydrogenase. A mechanism for adaptation to the intracellular environment. J Biol Chem. 1985;260:10563-8 pubmed
    ..The gene for isocitrate dehydrogenase kinase/phosphatase (aceK) was located in the glyoxylate bypass operon, downstream from the genes for isocitrate lyase and malate synthase.
  4. 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. ..
  5. 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. ..
  6. 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
    ..The structural gene encoding ICDH kinase/phosphatase (aceK) together with those encoding ICL (aceA) and MS (aceB) form an operon (aceBAK; otherwise known as the ace operon) ..
  7. 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
    ..Neither threonine nor tyrosine, when substituted for the serine at the phosphorylation site, is detectably phosphorylated by isocitrate dehydrogenase kinase. ..
  8. Phue J, Noronha S, Hattacharyya R, Wolfe A, Shiloach J. Glucose metabolism at high density growth of E. coli B and E. coli K: differences in metabolic pathways are responsible for efficient glucose utilization in E. coli B as determined by microarrays and Northern blot analyses. Biotechnol Bioeng. 2005;90:805-20 pubmed
    ..The gluconeogenesis pathway (fbp, pckA, and ppsA) which leads to glycogen accumulation is constitutively active in E. coli BL21 regardless of glucose feeding strategy. ..
  9. Stueland C, Ikeda T, LaPorte D. Mutation of the predicted ATP binding site inactivates both activities of isocitrate dehydrogenase kinase/phosphatase. J Biol Chem. 1989;264:13775-9 pubmed
    ..detectable IDH kinase activity as measured in vitro, the mutant allele retained the ability to complement an aceK deletion mutation, restoring the ability of these cells to grow on minimal acetate medium...

More Information


  1. 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. ..
  2. LaPorte D, Chung T. A single gene codes for the kinase and phosphatase which regulate isocitrate dehydrogenase. J Biol Chem. 1985;260:15291-7 pubmed
    The gene which codes for isocitrate dehydrogenase kinase/phosphatase of Escherichia coli, aceK, has been cloned...
  3. Yamamoto K, Ishihama A. Two different modes of transcription repression of the Escherichia coli acetate operon by IclR. Mol Microbiol. 2003;47:183-94 pubmed
    ..which encodes isocitrate lyase (aceB), malate synthase (aceA) and isocitrate dehydroge-nase kinase/phosphorylase (aceK) in the glyoxylate bypass. IclR also represses the expression of iclR in an autogenous manner...
  4. Stueland C, Eck K, Stieglbauer K, LaPorte D. Isocitrate dehydrogenase kinase/phosphatase exhibits an intrinsic adenosine triphosphatase activity. J Biol Chem. 1987;262:16095-9 pubmed
    ..Even in the presence of near-saturating concentrations of phospho-IDH, the rate of ATP hydrolysis was 4-fold greater than the rate of the cyclic phosphorylation of IDH. ..
  5. Oudot C, Cortay J, Blanchet C, LaPorte D, di Pietro A, Cozzone A, et al. The "catalytic" triad of isocitrate dehydrogenase kinase/phosphatase from E. coli and its relationship with that found in eukaryotic protein kinases. Biochemistry. 2001;40:3047-55 pubmed
    ..the recovered mutant enzymes were barely able to phosphorylate IDH either in vitro or after expression in an aceK (-) mutant strain...
  6. Cortay J, Bleicher F, Rieul C, Reeves H, Cozzone A. Nucleotide sequence and expression of the aceK gene coding for isocitrate dehydrogenase kinase/phosphatase in Escherichia coli. J Bacteriol. 1988;170:89-97 pubmed
    ..The aceK gene coding for this enzyme is part of the polycistronic ace operon, which also includes the aceB and aceA genes ..
  7. Cortay J, Bleicher F, Duclos B, Cenatiempo Y, Gautier C, Prato J, et al. Utilization of acetate in Escherichia coli: structural organization and differential expression of the ace operon. Biochimie. 1989;71:1043-9 pubmed
    ..respectively for malate synthase (aceB), isocitrate lyase (aceA) and isocitrate dehydrogenase kinase/phosphatase (aceK), and the surrounding genes iclR and metA...
  8. LaPorte D. The isocitrate dehydrogenase phosphorylation cycle: regulation and enzymology. J Cell Biochem. 1993;51:14-8 pubmed
    ..The picture which has emerged is one of an exquisitely sensitive and flexible system which is capable of adapting efficiently to the environment both inside and outside the cell. ..
  9. Rittinger K, Negre D, Divita G, Scarabel M, Bonod Bidaud C, Goody R, et al. Escherichia coli isocitrate dehydrogenase kinase/phosphatase. Overproduction and kinetics of interaction with its substrates by using intrinsic fluorescence and fluorescent nucleotide analogues. Eur J Biochem. 1996;237:247-54 pubmed
    The aceK gene of Escherichia coli, which encodes the isocitrate dehydrogenase kinase/phosphatase (IDH K/P), was cloned in the pQE30 expression vector to overproduce a protein tagged with six histidine residues at its N-terminus...
  10. Galinier A, Bleicher F, Negre D, Perrière G, Duclos B, Cozzone A, et al. Primary structure of the intergenic region between aceK and iclR in the Escherichia coli chromosome. Gene. 1991;97:149-50 pubmed
  11. Ikeda T, LaPorte D. Isocitrate dehydrogenase kinase/phosphatase: aceK alleles that express kinase but not phosphatase activity. J Bacteriol. 1991;173:1801-6 pubmed
    ..This phosphorylation cycle is catalyzed by a bifunctional enzyme, IDH kinase/phosphatase, which is encoded by aceK. We have employed random mutagenesis to isolate novel alleles of aceK...
  12. Matsuoka M, McFadden B. Isolation, hyperexpression, and sequencing of the aceA gene encoding isocitrate lyase in Escherichia coli. J Bacteriol. 1988;170:4528-36 pubmed
    ..8-kilodalton subunit of the castor bean enzyme with 39% identity except for limited N- and C-terminal regions and a 103-residue stretch that was unique for the plant enzyme and started approximately in the middle of that peptide. ..
  13. Walsh K, Koshland D. Determination of flux through the branch point of two metabolic cycles. The tricarboxylic acid cycle and the glyoxylate shunt. J Biol Chem. 1984;259:9646-54 pubmed
  14. Zheng J, Ji A, Jia Z. Purification, crystallization and preliminary X-ray analysis of bifunctional isocitrate dehydrogenase kinase/phosphatase in complex with its substrate, isocitrate dehydrogenase, from Escherichia coli. Acta Crystallogr Sect F Struct Biol Cryst Commun. 2009;65:1153-6 pubmed publisher
    ..phosphorylated and dephosphorylated by a single bifunctional protein, isocitrate dehydrogenase kinase/phosphatase (AceK), which is encoded by the aceK gene...
  15. LaPorte D, Stueland C, Ikeda T. Isocitrate dehydrogenase kinase/phosphatase. Biochimie. 1989;71:1051-7 pubmed
    ..IDH kinase/phosphatase is expressed from a single gene, aceK, and both activities are catalyzed by the same polypeptide...
  16. el Mansi E, Mackintosh C, Duncan K, Holms W, Nimmo H. Molecular cloning and over-expression of the glyoxylate bypass operon from Escherichia coli ML308. Biochem J. 1987;242:661-5 pubmed
    ..operon, namely malate synthase A (aceB), isocitrate lyase (aceA) and isocitrate dehydrogenase kinase/phosphatase (aceK), as judged by overexpression of enzyme activities and transcription/translation experiments in vitro...
  17. Varela I, Nimmo H. Photoaffinity labelling shows that Escherichia coli isocitrate dehydrogenase kinase/phosphatase contains a single ATP-binding site. FEBS Lett. 1988;231:361-5 pubmed
    ..ATP and ADP protected the two activities to similar extents. The data suggest that the activation of the phosphatase by adenine nucleotides results from binding of the nucleotides to the active site of the kinase. ..
  18. Shinar G, Rabinowitz J, Alon U. Robustness in glyoxylate bypass regulation. PLoS Comput Biol. 2009;5:e1000297 pubmed publisher
    ..Instead, we suggest a robust mechanism where both substrates bind the bifunctional enzyme to form a ternary complex. ..
  19. Zheng J, Lee D, Jia Z. Purification, crystallization and preliminary X-ray analysis of isocitrate dehydrogenase kinase/phosphatase from Escherichia coli. Acta Crystallogr Sect F Struct Biol Cryst Commun. 2009;65:536-9 pubmed publisher
    The Escherichia coli aceK gene encodes isocitrate dehydrogenase kinase/phosphatase (EC 2.7.11...
  20. Yates S, Edwards T, Bryan C, Stein A, Van Voorhis W, Myler P, et al. Structural basis of the substrate specificity of bifunctional isocitrate dehydrogenase kinase/phosphatase. Biochemistry. 2011;50:8103-6 pubmed publisher
    Isocitrate dehydrogenase kinase/phosphatase (AceK) regulates entry into the glyoxylate bypass by reversibly phosphorylating isocitrate dehydrogenase (ICDH)...
  21. Miller S, Chen R, Karschnia E, Romfo C, Dean A, LaPorte D. Locations of the regulatory sites for isocitrate dehydrogenase kinase/phosphatase. J Biol Chem. 2000;275:833-9 pubmed
  22. Oudot C, Jaquinod M, Cortay J, Cozzone A, Jault J. The isocitrate dehydrogenase kinase/phosphatase from Escherichia coli is highly sensitive to in-vitro oxidative conditions role of cysteine67 and cysteine108 in the formation of a disulfide-bonded homodimer. Eur J Biochem. 1999;262:224-9 pubmed
    ..Previous results have shown that this additional Cys356-Cys480 disulfide bond is intramolecular [Oudot, C., Jault, J.-M., Jaquinod, M., Negre, D., Prost, J.-F., Cozzone, A.J. & Cortay, J.-C. (1998) Eur. J. Biochem. 258, 579-585]. ..
  23. 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. ..
  24. McKee J, Hlodan R, Nimmo H. Studies of the phosphorylation of Escherichia coli isocitrate dehydrogenase. Recognition of the enzyme by isocitrate dehydrogenase kinase/phosphatase and effects of phosphorylation on its structure and properties. Biochimie. 1989;71:1059-64 pubmed
    ..The kinase activity of this enzyme can phosphorylate intact isocitrate dehydrogenase but not proteolytic fragments derived from it, nor a synthetic peptide corresponding to the sequence round the phosphorylation site. ..
  25. Chung T, Resnik E, Stueland C, LaPorte D. Relative expression of the products of glyoxylate bypass operon: contributions of transcription and translation. J Bacteriol. 1993;175:4572-5 pubmed
    ..translation and premature transcriptional termination contributed to the downshift in expression between aceA and aceK. Premature transcriptional termination occurred within aceK and appears to result from inefficient translation...
  26. Ikeda T, Houtz E, LaPorte D. Isocitrate dehydrogenase kinase/phosphatase: identification of mutations which selectively inhibit phosphatase activity. J Bacteriol. 1992;174:1414-6 pubmed
    Mutations in aceK, the gene encoding isocitrate dehydrogenase kinase/phosphatase, which selectively inhibit phosphatase activity have been isolated...
  27. Gui L, Sunnarborg A, LaPorte D. Regulated expression of a repressor protein: FadR activates iclR. J Bacteriol. 1996;178:4704-9 pubmed
    ..We observed a similar increase when we inactivated the FadR binding site of an iclR+ allele. This result suggests that FadR regulates aceBAK indirectly by altering the expression of IclR. ..
  28. Chung T, Klumpp D, LaPorte D. Glyoxylate bypass operon of Escherichia coli: cloning and determination of the functional map. J Bacteriol. 1988;170:386-92 pubmed
    ..from aceA and aceB, and the regulatory enzyme, isocitrate dehydrogenase kinase/phosphatase, is expressed from aceK. We cloned this operon and determined its functional map by deletion analysis...
  29. Nimmo G, Borthwick A, Holms W, Nimmo H. Partial purification and properties of isocitrate dehydrogenase kinase/phosphatase from Escherichia coli ML308. Eur J Biochem. 1984;141:401-8 pubmed
    ..The extent of the interconversion correlated well with the changes in isocitrate dehydrogenase activity. ..
  30. Cosloy S. D-serine transport system in Escherichia coli K-12. J Bacteriol. 1973;114:679-84 pubmed
    ..The transport mutation appears to be multistep and maps to the right of malB on the E. coli linkage map. ..
  31. Klumpp D, Plank D, Bowdin L, Stueland C, Chung T, LaPorte D. Nucleotide sequence of aceK, the gene encoding isocitrate dehydrogenase kinase/phosphatase. J Bacteriol. 1988;170:2763-9 pubmed
    ..We have determined the nucleotide sequence of aceK, the gene encoding IDH kinase/phosphatase...
  32. Zheng J, Jia Z. Structure of the bifunctional isocitrate dehydrogenase kinase/phosphatase. Nature. 2010;465:961-5 pubmed publisher
    The Escherichia coli isocitrate dehydrogenase kinase/phosphatase (AceK) is a unique bifunctional enzyme that phosphorylates or dephosphorylates isocitrate dehydrogenase (ICDH) in response to environmental changes, resulting in the ..