The Emergence of 2-Oxoglutarate as a Master Regulator Metabolite

Microbiology and Molecular Biology Reviews

Volumn 79, Issue 4, 2015, Pages 419-435

  Huergo, Luciano F ^a   Dixon, Ray ^b  

^a FEDERAL UNIVERSITY OF PARANÁ   (Brazil)

^b JOHN INNES CENTRE   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

2 OXOGLUTARIC ACID; ACETYL COENZYME A CARBOXYLASE; BACTERIAL PROTEIN; CARBOHYDRATE; CYCLIC AMP; NITROGEN REGULATORY PROTEIN; NITROGENASE; PHOSPHOTRANSFERASE; PROTEIN NIFA; PROTEIN NRPR; PROTEIN NTCA; REGULATOR PROTEIN; UNCLASSIFIED DRUG; ALPHA-KETOGLUTARIC ACID; CARBON; NITROGEN; PHOSPHOENOLPYRUVATE SUGAR PHOSPHOTRANSFERASE; TRANSCRIPTION FACTOR;

ARCHAEON; CARBON METABOLISM; CITRIC ACID CYCLE; CYANOBACTERIUM; ENERGY YIELD; ENZYME PHOSPHORYLATION; ENZYME REGULATION; ESCHERICHIA COLI; EUKARYOTE; METABOLIC REGULATION; METABOLITE; NITROGEN AVAILABILITY; NITROGEN FIXATION; NONHUMAN; NUTRITIONAL STATUS; REVIEW; TRANSCRIPTION REGULATION; ENERGY METABOLISM; GENETICS; METABOLISM; SIGNAL TRANSDUCTION;

ARCHAEA; CARBON; CITRIC ACID CYCLE; CYANOBACTERIA; ENERGY METABOLISM; ESCHERICHIA COLI; KETOGLUTARIC ACIDS; METABOLIC NETWORKS AND PATHWAYS; NITROGEN; PHOSPHOENOLPYRUVATE SUGAR PHOSPHOTRANSFERASE SYSTEM; SIGNAL TRANSDUCTION; TRANSCRIPTION FACTORS;

EID: 84948395539     PISSN: 10922172     EISSN: 10985557     Source Type: Journal    
DOI: 10.1128/MMBR.00038-15     Document Type: Review

References (168)

1. Commichau FM, Forchhammer K, Stulke J. 2006. Regulatory links between carbon and nitrogen metabolism. Curr Opin Microbiol 9:167-172. http://dx.doi.org/10.1016/j.mib.2006.01.001.
2. Tian J, Bryk R, Shi S, Erdjument-Bromage H, Tempst P, Nathan C. 2005. Mycobacteriumtuberculosisappearstolackalpha-ketoglutaratedehydrogenase and encodes pyruvate dehydrogenase in widely separated genes. Mol Microbiol 57:859-868. http://dx.doi.org/10.1111/j.1365-2958.2005.04741.x.
3. Zhang S, Bryant DA. 2011. The tricarboxylic acid cycle in cyanobacteria. Science 334:1551-1553. http://dx.doi.org/10.1126/science.1210858.
4. Xiong W, Brune D, Vermaas WF. 2014. The gamma-aminobutyric acid shunt contributes to closing the tricarboxylic acid cycle in Synechocystis sp. PCC 6803. Mol Microbiol 93:786-796. http://dx.doi.org/10.1111/mmi .12699.
5. Reitzer L. 2003. Nitrogen assimilation and global regulation in Escherichia coli. Annu Rev Microbiol 57:155-176. http://dx.doi.org/10.1146/annurev.micro.57.030502.090820.
6. Magasanik B. 1982. Genetic control in nitrogen assimilation in bacteria. Annu Rev Genet 16:135-168. http://dx.doi.org/10.1146/annurev.ge.16 .120182.001031.
7. Sharkey MA, Engel PC. 2008. Apparent negative co-operativity and substrate inhibition in overexpressed glutamate dehydrogenase from Escherichia coli. FEMS Microbiol Lett 281:132-139. http://dx.doi.org/10 .1111/j.1574-6968.2008.01086.x.
8. Alibhai M, Villafranca JJ. 1994. Kinetic and mutagenic studies of the role of the active site residues Asp-50 and Glu-327 of Escherichia coli glutamine synthetase. Biochemistry 33:682-686. http://dx.doi.org/10 .1021/bi00169a008.
9. Yuan J, Doucette CD, Fowler WU, Feng XJ, Piazza M, Rabitz HA, Wingreen NS, Rabinowitz JD. 2009. Metabolomics-driven quantitative analysis of ammonia assimilation in E. coli. Mol Syst Biol 5:302. http://dx .doi.org/10.1038/msb.2009.60.
10. Mantsala P, Zalkin H. 1976. Glutamate synthase. Properties of the glutamine-dependent activity. J Biol Chem 251:3294-3299.
11. Veronese FM, Boccu E, Conventi L. 1975. Glutamate dehydrogenase from Escherichia coli: induction, purification and properties of the enzyme. Biochim Biophys Acta 377:217-228. http://dx.doi.org/10.1016/0005-2744(75)90304-6.
12. Bennett BD, Yuan J, Kimball EH, Rabinowitz JD. 2008. Absolute quantitation of intracellular metabolite concentrations by an isotope ratio-based approach. Nat Protoc 3:1299-1311. http://dx.doi.org/10.1038/nprot.2008.107.
13. Yan D, Lenz P, Hwa T. 2011. Overcoming fluctuation and leakage problems in the quantification of intracellular 2-oxoglutarate levels in Escherichia coli. Appl Environ Microbiol 77:6763-6771. http://dx.doi .org/10.1128/AEM.05257-11.
14. Rabinowitz JD, Kimball E. 2007. Acidic acetonitrile for cellular metabolome extraction from Escherichia coli. Anal Chem 79:6167-6173. http://dx.doi.org/10.1021/ac070470c.
15. Cayley S, Lewis BA, Guttman HJ, Record MT, Jr. 1991. Characterization of the cytoplasm of Escherichia coli K-12 as a function of external osmolarity. Implications for protein-DNA interactions in vivo. J Mol Biol 222:281-300.
16. Senior PJ. 1975. Regulation of nitrogen metabolism in Escherichia coli and Klebsiella aerogenes: studies with the continuous culture technique. J Bacteriol 123:407.
17. Reyes-Ramirez F, Little R, Dixon R. 2001. Role of Escherichia coli nitrogen regulatory genes in the nitrogen response of the Azotobacter vinelandii NifL-NifA complex. J Bacteriol 183:3076-3082. http://dx.doi .org/10.1128/JB.183.10.3076-3082.2001.
18. Radchenko MV, Thornton J, Merrick M. 2010. Control of AmtB-GlnK complex formation by intracellular levels of ATP, ADP, and 2-oxoglutarate. J Biol Chem 285:31037-31045. http://dx.doi.org/10.1074/jbc.M110 .153908.
19. Brauer MJ, Yuan J, Bennett BD, Lu W, Kimball E, Botstein D, Rabinowitz JD. 2006. Conservation of the metabolomic response to starvation across two divergent microbes. Proc Natl Acad Sci U S A 103:19302-19307. http://dx.doi.org/10.1073/pnas.0609508103.
20. Schumacher J, Behrends V, Pan Z, Brown DR, Heydenreich F, Lewis MR, Bennett MH, Razzaghi B, Komorowski M, Barahona M, Stumpf MP, Wigneshweraraj S, Bundy JG, Buck M. 2013. Nitrogen and carbon status are integrated at the transcriptional level by the nitrogen regulator NtrC in vivo. mBio 4:e00881-13. http://dx.doi.org/10.1128/mBio.00881-13.
21. Zimmermann M, Sauer U, Zamboni N. 2014. Quantification and mass isotopomer profiling of alpha-keto acids in central carbon metabolism. Anal Chem 86:3232-3237. http://dx.doi.org/10.1021/ac500472c.
22. Zhang C, Wei ZH, Ye BC. 2013. Quantitative monitoring of 2-oxoglutarate in Escherichia coli cells by a fluorescence resonance energy transferbased biosensor. Appl Microbiol Biotechnol 97:8307-8316. http://dx .doi.org/10.1007/s00253-013-5121-5.
23. Chen HL, Bernard CS, Hubert P, My L, Zhang CC. 2013. Fluorescence resonance energy transfer based on interaction of PII and PipX proteins provides a robust and specific biosensor for 2-oxoglutarate, a central metabolite and a signaling molecule. FEBS J http://dx.doi.org/10.1111/j .1742-4658.2013.12702.x.24428626.
24. Luddecke J, Forchhammer K. 2013. From PII signaling to metabolite sensing: A novel 2-oxoglutarate sensor that details PII-NAGK complex formation. PLoS One 8:e83181. http://dx.doi.org/10.1371/journal.pone .0083181.
25. Dodsworth JA, Cady NC, Leigh JA. 2005. 2-Oxoglutarate and the PII homologues NifI1 and NifI2 regulate nitrogenase activity in cell extracts of Methanococcus maripaludis. Mol Microbiol 56:1527-1538. http://dx .doi.org/10.1111/j.1365-2958.2005.04621.x.
26. Muro-Pastor MI, Reyes JC, Florencio FJ. 2001. Cyanobacteria perceive nitrogen status by sensing intracellular 2-oxoglutarate levels. J Biol Chem 276:38320-38328.
27. Laurent S, Chen H, Bedu S, Ziarelli F, Peng L, Zhang CC. 2005. Nonmetabolizable analogue of 2-oxoglutarate elicits heterocyst differentiation under repressive conditions in Anabaena sp. PCC 7120. Proc Natl Acad Sci U S A 102:9907-9912.
28. Sauer U, Eikmanns BJ. 2005. The PEP-pyruvate-oxaloacetate node as the switch point for carbon flux distribution in bacteria. FEMS Microbiol Rev 29:765-794. http://dx.doi.org/10.1016/j.femsre.2004.11.002.
29. Cozzone AJ, El-Mansi M. 2005. Control of isocitrate dehydrogenase catalytic activity by protein phosphorylation in Escherichia coli. J Mol Microbiol Biotechnol 9:132-146. http://dx.doi.org/10.1159/000089642.
30. Seol W, Shatkin AJ. 1991. Escherichia coli kgtP encodes an alphaketoglutarate transporter. Proc Natl Acad Sci U S A 88:3802-3806. http://dx.doi.org/10.1073/pnas.88.9.3802.
31. Zhang C, Ye BC. 2014. A single fluorescent protein-based sensor for in vivo 2-oxogluatarate detection in cell. Biosens Bioelectron 54:15-19. http://dx.doi.org/10.1016/j.bios.2013.10.038.
32. Guo W, Cai LL, Zou HS, Ma WX, Liu XL, Zou LF, Li YR, Chen XB, Chen GY. 2012. Ketoglutarate transport protein KgtP is secreted through the type III secretion system and contributes to virulence in Xanthomonas oryzae pv. oryzae. Appl Environ Microbiol 78:5672-5681. http://dx.doi.org/10.1128/AEM.07997-11.
33. Chubukov V, Sauer U. 2014. Environmental dependence of stationary-phase metabolism in Bacillus subtilis and Escherichia coli. Appl Environ Microbiol 80:2901-2909. http://dx.doi.org/10.1128/AEM.00061-14.
34. Adler SP, Purich D, Stadtman ER. 1975. Cascade control of Escherichia coli glutamine synthetase. Properties of the PII regulatory protein and the uridylyltransferase-uridylyl-removing enzyme. J Biol Chem 250:6264-6272.
35. Sant'Anna F, Trentini D, Weber SD, Cecagno R, da Silva SC, Schrank I. 2009. The PII superfamily revised: A novel group and evolutionary insights. J Mol Evol 68:322-336. http://dx.doi.org/10.1007/s00239-009-9209-6.
36. Huergo LF, Pedrosa FO, Muller-Santos M, Chubatsu LS, Monteiro RA, Merrick M, Souza EM. 2012. PII signal transduction proteins: pivotal players in post-translational control of nitrogenase activity. Microbiology 158:176-190. http://dx.doi.org/10.1099/mic.0.049783-0.
37. Huergo LF, Chandra G, Merrick M. 2013. P(II) signal transduction proteins: nitrogen regulation and beyond. FEMS Microbiol Rev 37:251-283. http://dx.doi.org/10.1111/j.1574-6976.2012.00351.x.
38. Forchhammer K. 2010. The network of P(II) signalling protein interactions in unicellular cyanobacteria. Adv Exp Med Biol 675:71-90. http://dx.doi.org/10.1007/978-1-4419-1528-3-5.
39. Jiang P, Ninfa AJ. 2009. Sensation and signaling of alpha-ketoglutarate and adenylylate energy charge by the Escherichia coli PII signal transduction protein require cooperation of the three ligand-binding sites within the PII trimer. Biochemistry 48:11522-11531. http://dx.doi.org/10.1021/bi9011594.
40. Truan D, Huergo LF, Chubatsu LS, Merrick M, Li XD, Winkler FK. 2010. A new P(II) protein structure identifies the 2-oxoglutarate binding site. J Mol Biol 400:531-539. http://dx.doi.org/10.1016/j.jmb.2010.05.036.
41. Truan D, Bjelic S, Li XD, Winkler FK. 2014. Structure and thermodynamics of effector molecule binding to the nitrogen signal transduction PII protein GlnZ from Azospirillum brasilense. J Mol Biol 426:2783-2799. http://dx.doi.org/10.1016/j.jmb.2014.05.008.
42. Jiang P, Peliska JA, Ninfa AJ. 1998. Enzymological characterization of the signal-transducing uridylyltransferase/uridylyl-removing enzyme (EC 2.7.7.59) of Escherichia coli and its interaction with the PII protein. Biochemistry 37:12782-12794. http://dx.doi.org/10.1021/bi980667m.
43. Jiang P, Ninfa AJ. 2007. Escherichia coli PII signal transduction protein controlling nitrogen assimilation acts as a sensor of adenylate energy charge in vitro. Biochemistry 46:12979-12996. http://dx.doi.org/10.1021/bi701062t.
44. Fokina O, Chellamuthu VR, Forchhammer K, Zeth K. 2010. Mechanism of 2-oxoglutarate signaling by the Synechococcus elongatus PII signal transduction protein. Proc Natl Acad Sci U S A 107:19760-19765. http://dx.doi.org/10.1073/pnas.1007653107.
45. Little R, Colombo V, Leech A, Dixon R. 2002. Direct interaction of the NifL regulatory protein with the GlnK signal transducer enables the Azotobacter vinelandii NifL-NifA regulatory system to respond to conditions replete for nitrogen. J Biol Chem 277:15472-15481. http://dx.doi.org/10 .1074/jbc.M112262200.
46. da Rocha RA, Weschenfelder TA, de Castilhos F, de Souza EM, Huergo LF, Mitchell DA. 2013. Mathematical model of the binding of allosteric effectors to the Escherichia coli PII signal transduction protein GlnB. Biochemistry 52:2683-2693. http://dx.doi.org/10.1021/bi301659r.
47. Gerhardt EC, Araujo LM, Ribeiro RR, Chubatsu LS, Scarduelli M, Rodrigues TE, Monteiro RA, Pedrosa FO, Souza EM, Huergo LF. 2012. Influence of the ADP/ATP ratio, 2-oxoglutarate and divalent ions on Azospirillum brasilense PII protein signalling. Microbiology 158: 1656-1663. http://dx.doi.org/10.1099/mic.0.058446-0.
48. Radchenko MV, Thornton J, Merrick M. 2013. PII signal transduction proteins are ATPases whose activity is regulated by 2-oxoglutarate. Proc Natl Acad Sci U S A 110:12948-12953. http://dx.doi.org/10.1073/pnas .1304386110.
49. Merrick M. 2014. Post-translational modification of P II signal transduction proteins. Front Microbiol 5:763. http://dx.doi.org/10.3389/fmicb.2014.00763.
50. Jiang P, Peliska JA, Ninfa AJ. 1998. The regulation of Escherichia coli glutamine synthetase revisited: role of 2-ketoglutarate in the regulation of glutamine synthetase adenylylation state. Biochemistry 37:12802-12810. http://dx.doi.org/10.1021/bi980666u.
51. Teixeira PF, Jonsson A, Frank M, Wang H, Nordlund S. 2008. Interaction of the signal transduction protein GlnJ with the cellular targets AmtB1, GlnE and GlnD in Rhodospirillum rubrum: dependence on manganese, 2-oxoglutarate and the ADP/ATP ratio. Microbiology 154: 2336-2347. http://dx.doi.org/10.1099/mic.0.2008/017533-0.
52. Bonatto AC, Souza EM, Oliveira MA, Monteiro RA, Chubatsu LS, Huergo LF, Pedrosa FO. 2012. Uridylylation of Herbaspirillum seropedicae GlnB and GlnK proteins is differentially affected by ATP, ADP and 2-oxoglutarate in vitro. Arch Microbiol 194:643-652. http://dx.doi.org/10.1007/s00203-012-0799-9.
53. Leigh JA, Dodsworth JA. 2007. Nitrogen regulation in bacteria and archaea. Annu Rev Microbiol 61:349-377. http://dx.doi.org/10.1146/annurev.micro.61.080706.093409.
54. Coutts G, Thomas G, Blakey D, Merrick M. 2002. Membrane sequestration of the signal transduction protein GlnK by the ammonium transporter AmtB. EMBO J 21:536-545. http://dx.doi.org/10.1093/emboj/21 .4.536.
55. Jiang P, Ninfa AJ. 1999. Regulation of autophosphorylation of Escherichia coli nitrogen regulator II by the PII signal transduction protein. J Bacteriol 181:1906-1911.
56. Gerhardt EC, Rodrigues TE, Muller-Santos M, Pedrosa FO, Souza EM, Forchhammer K, Huergo LF. 2015. The bacterial signal transduction protein GlnB regulates the committed step in fatty acid biosynthesis by acting as a dissociable regulatory subunit of acetyl-CoA carboxylase. Mol Microbiol 95:1025-1035. http://dx.doi.org/10.1111/mmi.12912.
57. Cronan JE, Jr, Waldrop GL. 2002. Multi-subunit acetyl-CoA carboxylases. Prog Lipid Res 41:407-435. http://dx.doi.org/10.1016/S0163-7827 (02)00007-3.
58. Tong L. 2013. Structure and function of biotin-dependent carboxylases. Cell Mol Life Sci 70:863-891. http://dx.doi.org/10.1007/s00018-012-1096-0.
59. Feria Bourrellier AB, Valot B, Guillot A, Ambard-Bretteville F, Vidal J, Hodges M. 2010. Chloroplast acetyl-CoA carboxylase activity is 2-oxoglutarate-regulated by interaction of PII with the biotin carboxyl carrier subunit. Proc Natl Acad Sci U S A 107:502-507. http://dx.doi.org/10.1073/pnas.0910097107.
60. Rodrigues TE, Gerhardt EC, Oliveira MA, Chubatsu LS, Pedrosa FO, Souza EM, Souza GA, Muller-Santos M, Huergo LF. 2014. Search for novel targets of the PII signal transduction protein in bacteria identifies the BCCP component of acetyl-CoA carboxylase as a PII binding partner. Mol Microbiol 91:751-761. http://dx.doi.org/10.1111/mmi.12493.
61. Baud S, Feria Bourrellier AB, Azzopardi M, Berger A, Dechorgnat J, Daniel-Vedele F, Lepiniec L, Miquel M, Rochat C, Hodges M, Ferrario-Mery S. 2010. PII is induced by WRINKLED1 and fine-tunes fatty acid composition in seeds of Arabidopsis thaliana. Plant J 64:291-303. http://dx.doi.org/10.1111/j.1365-313X.2010.04332.x.
62. Dixon R, Kahn D. 2004. Genetic regulation of biological nitrogen fixation. Nat Rev Microbiol 2:621-631. http://dx.doi.org/10.1038/nrmicro954.
63. Martinez-Argudo I, Little R, Shearer N, Johnson P, Dixon R. 2004. The NifL-NifA system: A multidomain transcriptional regulatory complex that integrates environmental signals. J Bacteriol 186:601-610. http://dx .doi.org/10.1128/JB.186.3.601-610.2004.
64. Slavny P, Little R, Salinas P, Clarke TA, Dixon R. 2010. Quaternary structure changes in a second Per-Arnt-Sim domain mediate intramolecular redox signal relay in the NifL regulatory protein. Mol Microbiol 75:61-75. http://dx.doi.org/10.1111/j.1365-2958.2009.06956.x.
65. Little R, Salinas P, Slavny P, Clarke TA, Dixon R. 2011. Substitutions in the redox-sensing PAS domain of the NifL regulatory protein define an inter-subunit pathway for redox signal transmission. Mol Microbiol 82:222-235. http://dx.doi.org/10.1111/j.1365-2958.2011.07812.x.
66. Rudnick P, Kunz C, Gunatilaka MK, Hines ER, Kennedy C. 2002. Role of GlnK in NifL-mediated regulation of NifA activity in Azotobacter vinelandii. J Bacteriol 184:812-820. http://dx.doi.org/10.1128/JB.184.3 .812-820.2002.
67. Little R, Reyes-Ramirez F, Zhang Y, van Heeswijk WC, Dixon R. 2000. Signal transduction to the Azotobacter vinelandii NifL-NifA regulatory system is influenced directly by interaction with 2-oxoglutarate and the PII regulatory protein. EMBO J 19:6041-6050. http://dx.doi.org/10 .1093/emboj/19.22.6041.
68. Little R, Dixon R. 2003. The amino-terminal GAF domain of Azotobacter vinelandii NifA binds 2-oxoglutarate to resist inhibition by NifL under nitrogen-limiting conditions. J Biol Chem 278:28711-28718. http://dx.doi.org/10.1074/jbc.M301992200.
69. Perry S, Shearer N, Little R, Dixon R. 2005. Mutational analysis of the nucleotide-binding domain of the anti-activator NifL. J Mol Biol 346: 935-949. http://dx.doi.org/10.1016/j.jmb.2004.12.033.
70. Martinez-Argudo I, Little R, Dixon R. 2004. Role of the amino-terminal GAF domain of the NifA activator in controlling the response to the antiactivator protein NifL. Mol Microbiol 52:1731-1744. http://dx.doi .org/10.1111/j.1365-2958.2004.04089.x.
71. Chen S, Liu L, Zhou X, Elmerich C, Ji-Lun L. 2005. Functional analysis of the GAF domain of NifA in Azospirillum brasilense: effects of Tyr-Phe mutations on NifA and its interaction with GlnB. Mol Genet Genomics 273:415-422. http://dx.doi.org/10.1007/s00438-005-1146-5.
72. Zou X, Zhu Y, Pohlmann EL, Li J, Zhang Y, Roberts GP. 2008. Identification and functional characterization of NifA variants that are independent of GlnB activation in the photosynthetic bacterium Rhodospirillum rubrum. Microbiology 154:2689-2699. http://dx.doi.org/10 .1099/mic.0.2008/019406-0.
73. Oliveira MA, Aquino B, Bonatto AC, Huergo LF, Chubatsu LS, Pedrosa FO, Souza EM, Dixon R, Monteiro RA. 2012. Interaction of GlnK with the GAF domain of Herbaspirillum seropedicae NifA mediates NH4-regulation. Biochimie 94:1041-1047. http://dx.doi.org/10.1016/j .biochi.2012.01.007.
74. Michel-Reydellet N, Kaminski PA. 1999. Azorhizobium caulinodans PII and GlnK proteins control nitrogen fixation and ammonia assimilation. J Bacteriol 181:2655-2658.
75. Drepper T, Gross S, Yakunin AF, Hallenbeck PC, Masepohl B, Klipp W. 2003. Role of GlnB and GlnK in ammonium control of both nitrogenase systems in the phototrophic bacterium Rhodobacter capsulatus. Microbiology 149:2203-2212. http://dx.doi.org/10.1099/mic.0.26235-0.
76. Vega-Palas MA, Flores E, Herrero A. 1992. NtcA, a global nitrogen regulator from the cyanobacterium Synechococcus that belongs to the Crp family of bacterial regulators. Mol Microbiol 6:1853-1859. http://dx.doi .org/10.1111/j.1365-2958.1992.tb01357.x.
77. Espinosa J, Rodriguez-Mateos F, Salinas P, Lanza VF, Dixon R, de la Cruz F, Contreras A. 2014. PipX, the coactivator of NtcA, is a global regulator in cyanobacteria. Proc Natl Acad Sci U S A 111:E2423-E2430. http://dx.doi.org/10.1073/pnas.1404097111.
78. Picossi S, Flores E, Herrero A. 2014. ChIP analysis unravels an exceptionally wide distribution of DNA binding sites for the NtcA transcription factor in a heterocyst-forming cyanobacterium. BMC Genomics 15:22. http://dx.doi.org/10.1186/1471-2164-15-22.
79. Tanigawa R, Shirokane M, Maeda SS, Omata T, Tanaka K, Takahashi H. 2002. Transcriptional activation of NtcA-dependent promoters of Synechococcus sp.PCC7942 by 2-oxoglutarate in vitro. Proc Natl Acad Sci U S A 99:4251-4255.
80. Vazquez-Bermudez MF, Herrero A, Flores E. 2002. 2-Oxoglutarate increases the binding affinity of the NtcA (nitrogen control) transcription factor for the Synechococcus glnA promoter. FEBS Lett 512:71-74. http://dx.doi.org/10.1016/S0014-5793(02)02219-6.
81. Valladares A, Flores E, Herrero A. 2008. Transcription activation by NtcA and 2-oxoglutarate of three genes involved in heterocyst differentiation in the cyanobacterium Anabaena sp. strain PCC 7120. J Bacteriol 190:6126-6133. http://dx.doi.org/10.1128/JB.00787-08.
82. Herrero A, Muro-Pastor AM, Flores E. 2001. Nitrogen control in cyanobacteria. J Bacteriol 183:411-425. http://dx.doi.org/10.1128/JB.183.2.411-425.2001.
83. Lee DJ, Minchin SD, Busby SJ. 2012. Activating transcription in bacteria. Annu Rev Microbiol 66:125-152. http://dx.doi.org/10.1146/annurev-micro-092611-150012.
84. Llacer JL, Espinosa J, Castells MA, Contreras A, Forchhammer K, Rubio V. 2010. Structural basis for the regulation of NtcA-dependent transcription by proteins PipX and PII. Proc Natl Acad Sci U S A 107: 15397-15402. http://dx.doi.org/10.1073/pnas.1007015107.
85. Zhao MX, Jiang YL, He YX, Chen YF, Teng YB, Chen Y, Zhang CC, Zhou CZ. 2010. Structural basis for the allosteric control of the global transcription factor NtcA by the nitrogen starvation signal 2-oxoglutarate. Proc Natl Acad Sci U S A 107:12487-12492. http://dx.doi.org/10 .1073/pnas.1001556107.
86. Popovych N, Tzeng SR, Tonelli M, Ebright RH, Kalodimos CG. 2009. Structural basis for cAMP-mediated allosteric control of the catabolite activator protein. Proc Natl Acad SciUSA106:6927-6932. http://dx.doi .org/10.1073/pnas.0900595106.
87. Sharma H, Yu S, Kong J, Wang J, Steitz TA. 2009. Structure of apo-CAP reveals that large conformational changes are necessary for DNA binding. Proc Natl Acad Sci U S A 106:16604-16609. http://dx.doi .org/10.1073/pnas.0908380106.
88. Forcada-Nadal A, Forchhammer K, Rubio V. 2014. SPR analysis of promoter binding of Synechocystis PCC6803 transcription factors NtcA and CRP suggests cross-talk and sheds light on regulation by effector molecules. FEBS Lett 588:2270-2276. http://dx.doi.org/10.1016/j.febslet .2014.05.010.
89. Liu X, Wang Y, Laurini E, Posocco P, Chen H, Ziarelli F, Janicki A, Qu F, Fermeglia M, Pricl S, Zhang CC, Peng L. 2013. Structural requirements of 2-oxoglutaric acid analogues to mimic its signaling function. Org Lett 15:4662-4665. http://dx.doi.org/10.1021/ol401914z.
90. Espinosa J, Forchhammer K, Burillo S, Contreras A. 2006. Interaction network in cyanobacterial nitrogen regulation: PipX, a protein that interacts in a 2-oxoglutarate dependent manner with PII and NtcA. Mol Microbiol 61:457-469. http://dx.doi.org/10.1111/j.1365-2958.2006.05231.x.
91. Burillo S, Luque I, Fuentes I, Contreras A. 2004. Interactions between the nitrogen signal transduction protein PII and N-acetyl glutamate kinase in organisms that perform oxygenic photosynthesis. J Bacteriol 186: 3346-3354. http://dx.doi.org/10.1128/JB.186.11.3346-3354.2004.
92. Zeth K, Fokina O, Forchhammer K. 2014. Structural basis and targetspecific modulation of ADP sensing by the Synechococcus elongatus PII signaling protein. J Biol Chem 289:8960-8972. http://dx.doi.org/10 .1074/jbc.M113.536557.
93. Espinosa J, Forchhammer K, Contreras A. 2007. Role of the Synechococcus PCC 7942 nitrogen regulator protein PipX in NtcA-controlled processes. Microbiology 153:711-718. http://dx.doi.org/10.1099/mic.0.2006/003574-0.
94. Zhao MX, Jiang YL, Xu BY, Chen Y, Zhang CC, Zhou CZ. 2010. Crystal structure of the cyanobacterial signal transduction protein PII in complex with PipX. J Mol Biol 402:552-559. http://dx.doi.org/10.1016/j .jmb.2010.08.006.
95. Lie TJ, Leigh JA. 2003. A novel repressor of nif and glnA expression in the methanogenic archaeon Methanococcus maripaludis. Mol Microbiol 47: 235-246.
96. Lie TJ, Wood GE, Leigh JA. 2005. Regulation of nif expression in Methanococcus maripaludis: roles of the euryarchaeal repressor NrpR, 2-oxoglutarate, and two operators. J Biol Chem 280:5236-5241. http://dx.doi.org/10.1074/jbc.M411778200.
97. Lie TJ, Dodsworth JA, Nickle DC, Leigh JA. 2007. Diverse homologues of the archaeal repressor NrpR function similarly in nitrogen regulation. FEMS Microbiol Lett 271:281-288. http://dx.doi.org/10.1111/j.1574-6968.2007.00726.x.
98. Weidenbach K, Ehlers C, Kock J, Ehrenreich A, Schmitz RA. 2008. Insights into the NrpR regulon in Methanosarcina mazei Go1. Arch Microbiol 190:319-332. http://dx.doi.org/10.1007/s00203-008-0369-3.
99. Weidenbach K, Ehlers C, Kock J, Schmitz RA. 2010. NrpRII mediates contacts between NrpRI and general transcription factors in the archaeon Methanosarcina mazei Go1. FEBS J 277:4398-4411. http://dx.doi .org/10.1111/j.1742-4658.2010.07821.x.
100. Wisedchaisri G, Dranow DM, Lie TJ, Bonanno JB, Patskovsky Y, Ozyurt SA, Sauder JM, Almo SC, Wasserman SR, Burley SK, Leigh JA, Gonen T. 2010. Structural underpinnings of nitrogen regulation by the prototypical nitrogen-responsive transcriptional factor NrpR. Structure 18:1512-1521. http://dx.doi.org/10.1016/j.str.2010.08.014.
101. Cases I, Velazquez F, de Lorenzo V. 2007. The ancestral role of the phosphoenolpyruvate-carbohydrate phosphotransferase system (PTS) as exposed by comparative genomics. Res Microbiol 158:666-670. http://dx.doi.org/10.1016/j.resmic.2007.08.002.
102. Deutscher J, Francke C, Postma PW. 2006. How phosphotransferase system-related protein phosphorylation regulates carbohydrate metabolism in bacteria. Microbiol Mol Biol Rev 70:939-1031. http://dx.doi.org/10.1128/MMBR.00024-06.
103. Deutscher J, Ake FM, Derkaoui M, Zebre AC, Cao TN, Bouraoui H, Kentache T, Mokhtari A, Milohanic E, Joyet P. 2014. The bacterial phosphoenolpyruvate:carbohydrate phosphotransferase system: regulation by protein phosphorylation and phosphorylation-dependent protein-protein interactions. Microbiol Mol Biol Rev 78:231-256. http://dx .doi.org/10.1128/MMBR.00001-14.
104. Weigel N, Kukuruzinska MA, Nakazawa A, Waygood EB, Roseman S. 1982. Sugar transport by the bacterial phosphotransferase system. Phosphoryl transfer reactions catalyzed by enzyme I of Salmonella typhimurium. J Biol Chem 257:14477-14491.
105. Postma PW, Lengeler JW, Jacobson GR. 1993. Phosphoenolpyruvate: carbohydrate phosphotransferase systems in bacteria. Microbiol Rev 57: 543-594.
106. Park YH, Lee BR, Seok YJ, Peterkofsky A. 2006. In vitro reconstitution of catabolite repression in Escherichia coli. J Biol Chem 281:6448-6454. http://dx.doi.org/10.1074/jbc.M512672200.
107. Gorke B, Stulke J. 2008. Carbon catabolite repression in bacteria: many ways to make the most out of nutrients. Nat Rev Microbiol 6:613-624. http://dx.doi.org/10.1038/nrmicro1932.
108. Doucette CD, Schwab DJ, Wingreen NS, Rabinowitz JD. 2011. Alphaketoglutarate coordinates carbon and nitrogen utilization via enzyme I inhibition. Nat Chem Biol 16:894-901. http://dx.doi.org/10.1038/nchembio .685.
109. Venditti V, Ghirlando R, Clore GM. 2013. Structural basis for enzyme I inhibition by alpha-ketoglutarate. ACS Chem Biol 8:1232-1240. http://dx.doi.org/10.1021/cb400027q.
110. Venditti V, Tugarinov V, Schwieters CD, Grishaev A, Clore GM. 2015. Large interdomain rearrangement triggered by suppression of micro-to millisecond dynamics in bacterial enzyme I. Nat Commun 6:5960. http://dx.doi.org/10.1038/ncomms6960.
111. Daniel J, Danchin A. 1986. 2-Ketoglutarate as a possible regulatory metabolite involved in cyclic AMP-dependent catabolite repression in Escherichia coli K12. Biochimie 68:303-310. http://dx.doi.org/10.1016/S0300-9084(86)80027-X.
112. You C, Okano H, Hui S, Zhang Z, Kim M, Gunderson CW, Wang YP, Lenz P, Yan D, Hwa T. 2013. Coordination of bacterial proteome with metabolism by cyclic AMP signalling. Nature 500:301-306. http://dx.doi .org/10.1038/nature12446.
113. Rabinowitz JD, Silhavy TJ. 2013. Systems biology: metabolite turns master regulator. Nature 500:283-284. http://dx.doi.org/10.1038/nature12544.
114. Powell BS, Court DL, Inada T, Nakamura Y, Michotey V, Cui X, Reizer A, Saier MH, Reizer J. 1995. Novel proteins of the phosphotransferase system encoded within the rpoN operon of Escherichia coli. J Biol Chem 270:4822-4839. http://dx.doi.org/10.1074/jbc.270.9.4822.
115. Pfluger-Grau K, Gorke B. 2010. Regulatory roles of the bacterial nitrogen-related phosphotransferase system. Trends Microbiol 18:205-214. http://dx.doi.org/10.1016/j.tim.2010.02.003.
116. Zimmer B, Hillmann A, Gorke B. 2008. Requirements for the phosphorylation of the Escherichia coli EIIANtr protein in vivo. FEMS Microbiol Lett 286:96-102. http://dx.doi.org/10.1111/j.1574-6968.2008.01262.x.
117. Merrick MJ, Coppard JR. 1989. Mutations in genes downstream of the rpoN gene (encoding →54) of Klebsiella pneumoniae affect expression from →54-dependent promoters. Mol Microbiol 3:1765-1775. http://dx .doi.org/10.1111/j.1365-2958.1989.tb00162.x.
118. Reizer J, Reizer A, Merrick MJ, Plunkett G, III, Rose DJ, Saier MH, Jr. 1996. Novel phosphotransferase-encoding genes revealed by analysis of the Escherichia coli genome: A chimeric gene encoding an enzyme I homologue that possesses a putative sensory transduction domain. Gene 181:103-108. http://dx.doi.org/10.1016/S0378-1119(96)00481-7.
119. Begley GS, Jacobson GR. 1994. Overexpression, phosphorylation, and growth effects of ORF162, a Klebsiella pneumoniae protein that is encoded by a gene linked to rpoN, the gene encoding →54. FEMS Microbiol Lett 119:389-394.
120. Ninfa AJ. 2011. Unnecessary signaling: poorly named? J Bacteriol 193: 4571-4573. http://dx.doi.org/10.1128/JB.05682-11.
121. Reaves ML, Rabinowitz JD. 2011. Characteristic phenotypes associated with ptsN-null mutants in Escherichia coli K-12 are absent in strains with functional ilvG. J Bacteriol 193:4576-4581. http://dx.doi.org/10.1128/JB .00325-11.
122. Lawther RP, Calhoun DH, Adams CW, Hauser CA, Gray J, Hatfield GW. 1981. Molecular basis of valine resistance in Escherichia coli K-12. Proc Natl Acad Sci U S A 78:922-925. http://dx.doi.org/10.1073/pnas.78 .2.922.
123. Soupene E, van Heeswijk WC, Plumbridge J, Stewart V, Bertenthal D, Lee H, Prasad G, Paliy O, Charernnoppakul P, Kustu S. 2003. Physiological studies of Escherichia coli strain MG1655: growth defects and apparent cross-regulation of gene expression. J Bacteriol 185:5611-5626. http://dx.doi.org/10.1128/JB.185.18.5611-5626.2003.
124. Lee CR, Park YH, Kim M, Kim YR, Park S, Peterkofsky A, Seok YJ. 2013. Reciprocal regulation of the autophosphorylation of enzyme INtr by glutamine and alpha-ketoglutarate in Escherichia coli. Mol Microbiol 88:473-485. http://dx.doi.org/10.1111/mmi.12196.
125. Goodwin RA, Gage DJ. 2014. Biochemical characterization of a nitrogen-type phosphotransferase system reveals that enzyme EI(Ntr) integrates carbon and nitrogen signaling in Sinorhizobium meliloti. J Bacteriol 196:1901-1907. http://dx.doi.org/10.1128/JB.01489-14.
126. Lee CR, Cho SH, Yoon MJ, Peterkofsky A, Seok YJ. 2007. Escherichia coli enzyme IIANtr regulates the K transporter TrkA. Proc Natl Acad Sci U S A 104:4124-4129. http://dx.doi.org/10.1073/pnas.0609897104.
127. Luttmann D, Heermann R, Zimmer B, Hillmann A, Rampp IS, Jung K, Gorke B. 2009. Stimulation of the potassium sensor KdpD kinase activity by interaction with the phosphotransferase protein IIA(Ntr) in Escherichia coli. Mol Microbiol 72:978-994. http://dx.doi.org/10.1111/j .1365-2958.2009.06704.x.
128. Prell J, Mulley G, Haufe F, White JP, Williams A, Karunakaran R, Downie JA, Poole PS. 2012. The PTS(Ntr) system globally regulates ATP-dependent transporters in Rhizobium leguminosarum. Mol Microbiol 84:117-129. http://dx.doi.org/10.1111/j.1365-2958.2012.08014.x.
129. Untiet V, Karunakaran R, Kramer M, Poole P, Priefer U, Prell J. 2013. ABCtransport is inactivated by the PTS(Ntr) under potassium limitation in Rhizobium leguminosarum 3841. PLoS One 8:e64682. http://dx.doi .org/10.1371/journal.pone.0064682.
130. Siebers A, Altendorf K. 1988. The K-translocating Kdp-ATPase from Escherichia coli. Purification, enzymatic properties and production of complex-and subunit-specific antisera. Eur J Biochem 178:131-140.
131. Rhoads DB, Waters FB, Epstein W. 1976. Cation transport in Escherichia coli. VIII. Potassium transport mutants. J Gen Physiol 67:325-341.
132. Lee CR, Cho SH, Kim HJ, Kim M, Peterkofsky A, Seok YJ. 2010. Potassium mediates Escherichia coli enzyme IIA(Ntr)-dependent regulation of sigma factor selectivity. Mol Microbiol 78:1468-1483. http://dx .doi.org/10.1111/j.1365-2958.2010.07419.x.
133. Gyaneshwar P, Paliy O, McAuliffe J, Jones A, Jordan MI, Kustu S. 2005. Lessons from Escherichia coli genes similarly regulated in response to nitrogen and sulfur limitation. Proc Natl Acad Sci U S A 102:3453-3458. http://dx.doi.org/10.1073/pnas.0500141102.
134. Gyaneshwar P, Paliy O, McAuliffe J, Popham DL, Jordan MI, Kustu S. 2005. Sulfur and nitrogen limitation in Escherichia coli K-12: specific homeostatic responses. J Bacteriol 187:1074-1090. http://dx.doi.org/10 .1128/JB.187.3.1074-1090.2005.
135. Mandel MJ, Silhavy TJ. 2005. Starvation for different nutrients in Escherichia coli results in differential modulation of RpoS levels and stability. J Bacteriol 187:434-442. http://dx.doi.org/10.1128/JB.187.2.434-442 .2005.
136. Peterson CN, Mandel MJ, Silhavy TJ. 2005. Escherichia coli starvation diets: essential nutrients weigh in distinctly. J Bacteriol 187:7549-7553. http://dx.doi.org/10.1128/JB.187.22.7549-7553.2005.
137. Zafar MA, Carabetta VJ, Mandel MJ, Silhavy TJ. 2014. Transcriptional occlusion caused by overlapping promoters. Proc Natl Acad Sci U S A 111:1557-1561. http://dx.doi.org/10.1073/pnas.1323413111.
138. Muriel-Millan LF, Moreno S, Romero Y, Bedoya-Perez LP, Castaneda M, Segura D, Espin G. 2015. The unphosphorylated EIIA(Ntr) protein represses the synthesis of alkylresorcinols in Azotobacter vinelandii. PLoS One 10:e0117184. http://dx.doi.org/10.1371/journal.pone.0117184.
139. Gunka K, Commichau FM. 2012. Control of glutamate homeostasis in Bacillus subtilis: A complex interplay between ammonium assimilation, glutamate biosynthesis and degradation. Mol Microbiol 85:213-224. http://dx.doi.org/10.1111/j.1365-2958.2012.08105.x.
140. Picossi S, Belitsky BR, Sonenshein AL. 2007. Molecular mechanism of the regulation of Bacillus subtilis gltAB expression by GltC. J Mol Biol 365:1298-1313. http://dx.doi.org/10.1016/j.jmb.2006.10.100.
141. Woodger FJ, Bryant DA, Price GD. 2007. Transcriptional regulation of the CO2-concentrating mechanism in a euryhaline, coastal marine cyanobacterium, Synechococcus sp. strain PCC 7002: role of NdhR/CcmR. J Bacteriol 189:3335-3347. http://dx.doi.org/10.1128/JB.01745-06.
142. Daley SM, Kappell AD, Carrick MJ, Burnap RL. 2012. Regulation of the cyanobacterial CO2-concentrating mechanism involves internal sensing of NADP and alpha-ketoglutarate levels by transcription factor CcmR. PLoS One 7:e41286. http://dx.doi.org/10.1371/journal.pone.0041286.
143. Cai W, Wannemuehler Y, Dell'anna G, Nicholson B, Barbieri NL, Kariyawasam S, Feng Y, Logue CM, Nolan LK, Li G. 2013. A novel two-component signaling system facilitates uropathogenic Escherichia coli's ability to exploit abundant host metabolites. PLoS Pathog 9:e1003428. http://dx.doi.org/10.1371/journal.ppat.1003428.
144. Chin RM, Fu X, Pai MY, Vergnes L, Hwang H, Deng G, Diep S, Lomenick B, Meli VS, Monsalve GC, Hu E, Whelan SA, Wang JX, Jung G, Solis GM, Fazlollahi F, Kaweeteerawat C, Quach A, Nili M, Krall AS, Godwin HA, Chang HR, Faull KF, Guo F, Jiang M, Trauger SA, Saghatelian A, Braas D, Christofk HR, Clarke CF, Teitell MA, Petrascheck M, Reue K, Jung ME, Frand AR, Huang J. 2014. The metabolite alpha-ketoglutarate extends lifespan by inhibiting ATP synthase and TOR. Nature 510:397-401. http://dx.doi.org/10.1038/nature13264.
145. Lewis GD, Farrell L, Wood MJ, Martinovic M, Arany Z, Rowe GC, Souza A, Cheng S, McCabe EL, Yang E, Shi X, Deo R, Roth FP, Asnani A, Rhee EP, Systrom DM, Semigran MJ, Vasan RS, Carr SA, Wang TJ, Sabatine MS, Clish CB, Gerszten RE. 2010. Metabolic signatures of exercise in human plasma. Sci Transl Med 2:33ra37. http://dx.doi.org/10 .1126/scitranslmed.3001006.
146. Brugnara L, Vinaixa M, Murillo S, Samino S, Rodriguez MA, Beltran A, Lerin C, Davison G, Correig X, Novials A. 2012. Metabolomics approach for analyzing the effects of exercise in subjects with type 1 diabetes mellitus. PLoS One 7:e40600. http://dx.doi.org/10.1371/journal .pone.0040600.
147. Lomenick B, Hao R, Jonai N, Chin RM, Aghajan M, Warburton S, Wang J, Wu RP, Gomez F, Loo JA, Wohlschlegel JA, Vondriska TM, Pelletier J, Herschman HR, Clardy J, Clarke CF, Huang J. 2009. Target identification using drug affinity responsive target stability (DARTS). Proc Natl Acad Sci U S A 106:21984-21989. http://dx.doi.org/10.1073/pnas.0910040106.
148. He W, Miao FJ, Lin DC, Schwandner RT, Wang Z, Gao J, Chen JL, Tian H, Ling L. 2004. Citric acid cycle intermediates as ligands for orphan G-protein-coupled receptors. Nature 429:188-193. http://dx.doi .org/10.1038/nature02488.
149. Tokonami N, Morla L, Centeno G, Mordasini D, Ramakrishnan SK, Nikolaeva S, Wagner CA, Bonny O, Houillier P, Doucet A, Firsov D. 2013.-Ketoglutarate regulates acid-base balance through an intrarenal paracrine mechanism. J Clin Invest 123:3166-3171. http://dx.doi.org/10 .1172/JCI67562.
150. Hodges M. 2002. Enzyme redundancy and the importance of 2-oxoglutarate in plant ammonium assimilation. J Exp Bot 53:905-916. http://dx .doi.org/10.1093/jexbot/53.370.905.
151. Araujo WL, Martins AO, Fernie AR, Tohge T. 2014. 2-Oxoglutarate: linking TCA cycle function with amino acid, glucosinolate, flavonoid, alkaloid, and gibberellin biosynthesis. Front Plant Sci 5:552. http://dx.doi .org/10.3389/fpls.2014.00552.
152. Feria Bourrellier AB, Ferrario-Mery S, Vidal J, Hodges M. 2009. Metabolite regulation of the interaction between Arabidopsis thaliana PII and N-acetyl-L-glutamate kinase. Biochem Biophys Res Commun 387: 700-704. http://dx.doi.org/10.1016/j.bbrc.2009.07.088.
153. Ferrario-Mery S, Besin E, Pichon O, Meyer C, Hodges M. 2006. The regulatory PII protein controls arginine biosynthesis in Arabidopsis. FEBS Lett 580: 2015-2020. http://dx.doi.org/10.1016/j.febslet.2006.02.075.
154. Chellamuthu VR, Ermilova E, Lapina T, Luddecke J, Minaeva E, Herrmann C, Hartmann MD, Forchhammer K. 2014. A widespread glutamine-sensing mechanism in the plant kingdom. Cell 159:1188-1199. http://dx.doi.org/10.1016/j.cell.2014.10.015.
155. Salminen A, Kaarniranta K, Hiltunen M, Kauppinen A. 2014. Krebs cycle dysfunction shapes epigenetic landscape of chromatin: novel insights into mitochondrial regulation of aging process. Cell Signal 26: 1598-1603. http://dx.doi.org/10.1016/j.cellsig.2014.03.030.
156. Carey BW, Finley LW, Cross JR, Allis CD, Thompson CB. 2015. Intracellular alpha-ketoglutarate maintains the pluripotency of embryonic stem cells. Nature 518:413-416. http://dx.doi.org/10.1038/nature13981.
157. Chubukov V, Gerosa L, Kochanowski K, Sauer U. 2014. Coordination of microbial metabolism. Nat Rev Microbiol 12:327-340. http://dx.doi .org/10.1038/nrmicro3238.
158. Tian ZX, Li QS, Buck M, Kolb A, Wang YP. 2001. The CRP-cAMP complex and downregulation of the glnAp2 promoter provides a novel regulatory linkage between carbon metabolism and nitrogen assimilation in Escherichia coli. Mol Microbiol 41:911-924.
159. Mao XJ, Huo YX, Buck M, Kolb A, Wang YP. 2007. Interplay between CRP-cAMP and PII-Ntr systems forms novel regulatory network between carbon metabolism and nitrogen assimilation in Escherichia coli. Nucleic Acids Res 35:1432-1440. http://dx.doi.org/10.1093/nar/gkl1142.
160. Howitt S, Udvardi M. 2000. Structure, function and regulation of ammonium transporters in plants. Biochim Biophys Acta 1465:152-170. http://dx.doi.org/10.1016/S0005-2736(00)00136-X.
161. Buurman ET, Teixeira de Mattos MJ, Neijssel OM. 1991. Futile cycling of ammonium ions via the high affinity potassium uptake system (Kdp) of Escherichia coli. Arch Microbiol 155:391-395.
162. Wei Y, Southworth TW, Kloster H, Ito M, Guffanti AA, Moir A, Krulwich TA. 2003. Mutational loss of a K and NH4 transporter affects the growth and endospore formation of alkaliphilic Bacillus pseudofirmus OF4. J Bacteriol 185:5133-5147. http://dx.doi.org/10.1128/JB .185.17.5133-5147.2003.
163. Hess DC, Lu W, Rabinowitz JD, Botstein D. 2006. Ammonium toxicity and potassium limitation in yeast. PLoS Biol 4:e351. http://dx.doi.org/10 .1371/journal.pbio.0040351.
164. Coskun D, Britto DT, Li M, Oh S, Kronzucker HJ. 2013. Capacity and plasticity of potassium channels and high-affinity transporters in roots of barley and Arabidopsis. Plant Physiol 162:496-511. http://dx.doi.org/10 .1104/pp.113.215913.
165. ten Hoopen F, Cuin TA, Pedas P, Hegelund JN, Shabala S, Schjoerring JK, Jahn TP. 2010. Competition between uptake of ammonium and potassium in barley and Arabidopsis roots: molecular mechanisms and physiological consequences. J Exp Bot 61:2303-2315. http://dx.doi.org/10.1093/jxb/erq057.
166. Kleiner D. 1993. NH4 transport systems, p 379-396. In Bakker EP (ed), Alkali cation transport systems in prokaryotes. CRC Press, Boca Raton, FL.
167. Boogerd FC, Ma H, Bruggeman FJ, van Heeswijk WC, Garcia-Contreras R, Molenaar D, Krab K, Westerhoff HV. 2011. AmtBmediated NH3 transport in prokaryotes must be active and as a consequence regulation of transport by GlnK is mandatory to limit futile cycling of NH4/NH3. FEBS Lett 585:23-28. http://dx.doi.org/10.1016/j .febslet.2010.11.055.
168. Wang Y, Assaf Z, Liu X, Ziarelli F, Latifi A, Lamrabet O, Quelever G, Qu F, Zhang CC, Peng L. 2014. A "click" chemistry constructed affinity system for 2-oxoglutaric acid receptors and binding proteins. Org Biomol Chem 12:6470-6475. http://dx.doi.org/10.1039/C4OB01005A.