A NAC for Regulating Metabolism: the Nitrogen Assimilation Control Protein (NAC) from Klebsiella pneumoniae

ABSTRACT The nitrogen assimilation control protein (NAC) is a LysR-type transcriptional regulator (LTTR) that is made under conditions of nitrogen-limited growth. NAC's synthesis is entirely dependent on phosphorylated NtrC from the two-component Ntr system and requires the unusual sigma factor σ54 for transcription of the nac gene. NAC activates the transcription of σ70-dependent genes whose products provide the cell with ammonia or glutamate. NAC represses genes whose products use ammonia and also represses its own transcription. In addition, NAC also subtly adjusts other cellular functions to keep pace with the supply of biosynthetically available nitrogen.

[1]  T. Blauwkamp,et al.  Nac‐mediated repression of the serA promoter of Escherichia coli , 2002, Molecular microbiology.

[2]  S. Kustu,et al.  Mechanism of Transcriptional Activation by NtrC , 1995 .

[3]  A. Khodursky,et al.  Nitrogen regulatory protein C-controlled genes of Escherichia coli: scavenging as a defense against nitrogen limitation. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[4]  T. Goss,et al.  The nitrogen assimilation control protein, NAC, is a DNA binding transcription activator in Klebsiella aerogenes , 1995, Journal of bacteriology.

[5]  W. Brill,et al.  Genetic control of histidine degradation in Salmonella typhimurium, strain LT-2. , 1969, The Journal of biological chemistry.

[6]  F. Neidhardt,et al.  REVERSAL OF THE GLUCOSE INHIBITION OF HISTIDASE BIOSYNTHESIS IN AEROBACTER AEROGENES , 1957, Journal of bacteriology.

[7]  T. Goss,et al.  Repression of Glutamate Dehydrogenase Formation in Klebsiella aerogenes Requires Two Binding Sites for the Nitrogen Assimilation Control Protein, NAC , 2002, Journal of bacteriology.

[8]  B. Magasanik,et al.  Role of glnA-linked genes in regulation of glutamine synthetase and histidase formation in Klebsiella aerogenes , 1982, Journal of bacteriology.

[9]  Ann M Stock,et al.  Two-component signal transduction. , 2000, Annual review of biochemistry.

[10]  R. Bender,et al.  The nac (Nitrogen Assimilation Control) Gene from Escherichia coli , 1998, Journal of bacteriology.

[11]  B. Tyler.  Regulation of the assimilation of nitrogen compounds. , 1978, Annual review of biochemistry.

[12]  Genetic Analysis of the Nitrogen Assimilation Control Protein from Klebsiella pneumoniae , 2010, Journal of bacteriology.

[13]  P. Nygaard,et al.  Genetic evidence for a repressor of synthesis of cytosine deaminase and purine biosynthesis enzymes in Escherichia coli , 1989, Journal of bacteriology.

[14]  R. Bender,et al.  The nac (nitrogen assimilation control) gene from Klebsiella aerogenes , 1993, Journal of bacteriology.

[15]  W. Brill,et al.  Genetic and metabolic control of histidase and urocanase in Salmonella typhimurium, strain 15-59. , 1969, The Journal of biological chemistry.

[16]  R. Bender,et al.  Expanded Role for the Nitrogen Assimilation Control Protein in the Response of Klebsiella pneumoniae to Nitrogen Stress , 2010, Journal of bacteriology.

[17]  J. Hirschman,et al.  Products of nitrogen regulatory genes ntrA and ntrC of enteric bacteria activate glnA transcription in vitro: evidence that the ntrA product is a sigma factor. , 1985, Proceedings of the National Academy of Sciences of the United States of America.

[18]  B. Magasanik,et al.  Regulatory mutations in the Klebsiella aerogenes structural gene for glutamine synthetase , 1977, Journal of bacteriology.

[19]  B. Magasanik,et al.  Resistance to catabolite repression of histidase and proline oxidase during nitrogen-limited growth of Klebsiella aerogenes. , 1971, The Journal of biological chemistry.

[20]  B. Magasanik,et al.  The degradation of histidine by Aerobacter aerogenes. , 1955, The Journal of biological chemistry.

[21]  R. Bender,et al.  Complex Regulation of Urease Formation from the Two Promoters of the ure Operon of Klebsiella pneumoniae , 2007, Journal of bacteriology.

[22]  B. Magasanik,et al.  Glutamine synthetase and the regulation of histidase formation in Klebsiella aerogenes. , 1973, The Journal of biological chemistry.

[23]  B. Magasanik,et al.  Regulation of the synthesis of enzymes responsible for glutamate formation in Klebsiella aerogenes. , 1973, The Journal of biological chemistry.

[24]  R. Bender,et al.  Direct Selection for P1-Sensitive Mutants of Enteric Bacteria , 1974, Journal of bacteriology.

[25]  A. Muro-Pastor,et al.  Regulation of gene expression by repressor localization: biochemical evidence that membrane and DNA binding by the PutA protein are mutually exclusive , 1997, Journal of bacteriology.

[26]  R. Bender,et al.  Two Roles for the Leucine-Responsive Regulatory Protein in Expression of the Alanine Catabolic Operon (dadAB) inKlebsiella aerogenes , 1999, Journal of bacteriology.

[27]  The LysR-Type Nitrogen Assimilation Control Protein Forms Complexes with Both Long and Short DNA Binding Sites in the Absence of Coeffectors , 2010, Journal of bacteriology.

[28]  B. Magasanik,et al.  Urease of Klebsiella aerogenes: control of its synthesis by glutamine synthetase , 1977, Journal of bacteriology.

[29]  P. Pomposiello,et al.  Activation of the Escherichia coli lacZ promoter by the Klebsiella aerogenes nitrogen assimilation control protein (NAC), a LysR family transcription factor , 1995, Journal of bacteriology.

[30]  R. Hausinger,et al.  Copyright � 1995, American Society for Microbiology Molecular Biology of Microbial Ureases , 1995 .

[31]  P. Pomposiello,et al.  Two Roles for the DNA Recognition Site of theKlebsiella aerogenes Nitrogen Assimilation Control Protein , 1998, Journal of bacteriology.

[32]  Isolation of a Negative Control Mutant of the Nitrogen Assimilation Control Protein, NAC, in Klebsiella aerogenes , 2003, Journal of bacteriology.

[33]  D. Tempest,et al.  Synthesis of glutamate in Aerobacter aerogenes by a hitherto unknown route. , 1970, The Biochemical journal.

[34]  S. Kustu,et al.  Salmonella typhimurium apparently perceives external nitrogen limitation as internal glutamine limitation. , 1996, Journal of molecular biology.

[35]  R. Bender,et al.  Regulation of hutUH operon expression by the catabolite gene activator protein-cyclic AMP complex in Klebsiella aerogenes , 1984, Journal of bacteriology.

[36]  S. Maddocks,et al.  Structure and function of the LysR-type transcriptional regulator (LTTR) family proteins. , 2008, Microbiology.

[37]  S. Maloy,et al.  Regulation of proline utilization in enteric bacteria: cloning and characterization of the Klebsiella put control region , 1991, Journal of bacteriology.

[38]  R. Bender,et al.  Role of the nac gene product in the nitrogen regulation of some NTR-regulated operons of Klebsiella aerogenes , 1990, Journal of bacteriology.

[39]  Ryan L. Frisch.  The role of the nitrogen assimilation control protein (NAC) in the respone of Klebsiella pneumoniae to nitrogen limitation , 2009 .

[40]  T. Goss,et al.  Roles of Glutamate Synthase, gltBD, and gltF in Nitrogen Metabolism of Escherichia coli and Klebsiella aerogenes , 2001, Journal of bacteriology.

[41]  Repression of the Klebsiella aerogenes nac promoter , 1995, Journal of bacteriology.

[42]  F. Bolivar,et al.  Determination of the nucleotide sequence for the glutamate synthase structural genes of Escherichia coli K-12. , 1987, Gene.

[43]  B. Magasanik,et al.  Effects of Auxotrophic Mutations on the Adaptation to Inositol Degradation in Aerobacter Aerogenes. ∗ , 1952, Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine.

[44]  R. Bender,et al.  In vitro transcription of the histidine utilization (hutUH) operon from Klebsiella aerogenes , 1991, Journal of bacteriology.

[45]  R. Bender,et al.  Cloning of the Klebsiella aerogenes nac gene, which encodes a factor required for nitrogen regulation of the histidine utilization (hut) operons in Salmonella typhimurium , 1990, Journal of bacteriology.

[46]  R. Bender,et al.  The product of the Klebsiella aerogenes nac (nitrogen assimilation control) gene is sufficient for activation of the hut operons and repression of the gdh operon , 1993, Journal of bacteriology.

[47]  R. Valentine,et al.  The mechanism of ammonia assimilation in nitrogen fixing bacteria , 2004, Archiv für Mikrobiologie.

[48]  S. Kustu,et al.  Protein kinase and phosphoprotein phosphatase activities of nitrogen regulatory proteins NTRB and NTRC of enteric bacteria: roles of the conserved amino-terminal domain of NTRC. , 1988, Proceedings of the National Academy of Sciences of the United States of America.

[49]  P. Rainey,et al.  Dual Involvement of CbrAB and NtrBC in the Regulation of Histidine Utilization in Pseudomonas fluorescens SBW25 , 2008, Genetics.

[50]  B. Magasanik,et al.  Transcription of glnA by purified Escherichia coli components: core RNA polymerase and the products of glnF, glnG, and glnL. , 1985, Proceedings of the National Academy of Sciences of the United States of America.

[51]  A. Ninfa,et al.  Activation of transcription initiation from the nac promoter of Klebsiella aerogenes , 1995, Journal of bacteriology.

[52]  Li-Mei Chen,et al.  Genetic Analysis, Using P22 Challenge Phage, of the Nitrogen Activator Protein DNA-Binding Site in the Klebsiella aerogenes put Operon , 1998, Journal of bacteriology.

[53]  R. Bender.  The role of the NAC protein in the nitrogen regulation of Klebsiella aerogenes , 1991, Molecular microbiology.

[54]  The Amino-Terminal 100 Residues of the Nitrogen Assimilation Control Protein (NAC) Encode All Known Properties of NAC from Klebsiella aerogenes and Escherichia coli , 1999, Journal of bacteriology.

[55]  B. Magasanik,et al.  Biochemical parameters of glutamine synthetase from Klebsiella aerogenes , 1977, Journal of bacteriology.

[56]  R. Bender,et al.  Bidirectional promoter in the hut(P) region of the histidine utilization (hut) operons from Klebsiella aerogenes , 1988, Journal of bacteriology.

[57]  B. Magasanik,et al.  N-formimino-L-glutamate formiminohydrolase of Aerobacter aerogenes. , 1965, The Journal of biological chemistry.

[58]  S. Clarke.  Nasal carriage of Staphylococcus aureus , 1957 .

[59]  B. Magasanik,et al.  The enzymatic degradation of urocanic acid. , 1958, The Journal of biological chemistry.

[60]  F. Ausubel.  Regulation of nitrogen fixation genes , 1984, Cell.

[61]  B. Magasanik,et al.  Genetic control of glutamine synthetase in Klebiella aerogenes , 1975, Journal of bacteriology.

[62]  B. Magasanik.  The metabolic control of histidine assimilation and dissimilation in Aerobacter aerogenes. , 1955, The Journal of biological chemistry.

[63]  J. Zaim,et al.  Identification of activating region (AR) of Escherichia coli LysR‐type transcription factor CysB and CysB contact site on RNA polymerase alpha subunit at the cysP promoter , 2004, Molecular microbiology.

[64]  R. Hausinger,et al.  Klebsiella aerogenes urease gene cluster: sequence of ureD and demonstration that four accessory genes (ureD, ureE, ureF, and ureG) are involved in nickel metallocenter biosynthesis , 1992, Journal of bacteriology.

[65]  B. Magasanik,et al.  Nitrogen regulation system of Klebsiella aerogenes: the nac gene , 1983, Journal of bacteriology.

[66]  D. Macphee,et al.  Transduction in Klebsiella , 1969, Nature.

[67]  R. Iwanicka-Nowicka,et al.  Functional Dissection of the LysR-type CysB Transcriptional Regulator , 2001, The Journal of Biological Chemistry.

[68]  P. Pomposiello,et al.  Growth Inhibition Caused by Overexpression of the Structural Gene for Glutamate Dehydrogenase (gdhA) fromKlebsiella aerogenes , 2001, Journal of bacteriology.

[69]  R. Bender,et al.  Properties of the NAC (Nitrogen Assimilation Control Protein)-Binding Site within the ureD Promoter of Klebsiella pneumoniae , 2010, Journal of bacteriology.

[70]  R. Bender,et al.  Nitrogen Regulation of the codBA (Cytosine Deaminase) Operon from Escherichia coli by the Nitrogen Assimilation Control Protein, NAC , 2003, Journal of bacteriology.

[71]  A. Ninfa,et al.  Covalent modification of the glnG product, NRI, by the glnL product, NRII, regulates the transcription of the glnALG operon in Escherichia coli. , 1986, Proceedings of the National Academy of Sciences of the United States of America.

[72]  F. Neidhardt,et al.  EFFECT OF MIXTURES OF SUBSTRATES ON THE BIOSYNTHESIS OF INDUCIBLE ENZYMES IN AEROBACTER AEROGENES , 1957, Journal of bacteriology.

[73]  T. Goss.  The ArgP Protein Stimulates the Klebsiella pneumoniae gdhA Promoter in a Lysine-Sensitive Manner , 2008, Journal of bacteriology.

[74]  D. Tempest,et al.  'Glutamine(amide):2-oxoglutarate amino transferase oxido-reductase (NADP); an enzyme involved in the synthesis of glutamate by some bacteria. , 1970, Journal of general microbiology.

[75]  M. Schell.  Molecular biology of the LysR family of transcriptional regulators. , 1993, Annual review of microbiology.

[76]  R. Bender,et al.  Importance of Tetramer Formation by the Nitrogen Assimilation Control Protein for Strong Repression of Glutamate Dehydrogenase Formation in Klebsiella pneumoniae , 2005, Journal of bacteriology.

[77]  B. Magasanik.  Catabolite repression. , 1961, Cold Spring Harbor symposia on quantitative biology.

[78]  R. Bender,et al.  Alanine Catabolism in Klebsiella aerogenes: Molecular Characterization of the dadAB Operon and Its Regulation by the Nitrogen Assimilation Control Protein , 1998, Journal of bacteriology.