This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow An erratum has been published
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Kurnasov, O. V.
Right arrow Articles by Osterman, A. L.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Kurnasov, O. V.
Right arrow Articles by Osterman, A. L.

 Previous Article  |  Next Article 

Journal of Bacteriology, December 2002, p. 6906-6917, Vol. 184, No. 24
0021-9193/02/$04.00+0     DOI: 10.1128/JB.184.24.6906-6917.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Ribosylnicotinamide Kinase Domain of NadR Protein: Identification and Implications in NAD Biosynthesis

Oleg V. Kurnasov,1 Boris M. Polanuyer,1,{dagger} Shubha Ananta,1 Roman Sloutsky,1,{ddagger} Annie Tam,2 Svetlana Y. Gerdes,1 and Andrei L. Osterman1*

Integrated Genomics, Inc., Chicago, Illinois 60612,1 Department of Chemistry and Chemical Biology, Cornell University, Ithaca, New York 148532

Received 16 May 2002/ Accepted 21 August 2002

NAD is an indispensable redox cofactor in all organisms. Most of the genes required for NAD biosynthesis in various species are known. Ribosylnicotinamide kinase (RNK) was among the few unknown (missing) genes involved with NAD salvage and recycling pathways. Using a comparative genome analysis involving reconstruction of NAD metabolism from genomic data, we predicted and experimentally verified that bacterial RNK is encoded within the 3' region of the nadR gene. Based on these results and previous data, the full-size multifunctional NadR protein (as in Escherichia coli) is composed of (i) an N-terminal DNA-binding domain involved in the transcriptional regulation of NAD biosynthesis, (ii) a central nicotinamide mononucleotide adenylyltransferase (NMNAT) domain, and (iii) a C-terminal RNK domain. The RNK and NMNAT enzymatic activities of recombinant NadR proteins from Salmonella enterica serovar Typhimurium and Haemophilus influenzae were quantitatively characterized. We propose a model for the complete salvage pathway from exogenous N-ribosylnicotinamide to NAD which involves the concerted action of the PnuC transporter and NRK, followed by the NMNAT activity of the NadR protein. Both the pnuC and nadR genes were proven to be essential for the growth and survival of H. influenzae, thus implicating them as potential narrow-spectrum drug targets.

* Corresponding author. Mailing address: Integrated Genomics, Inc., 2201 W. Campbell Park Dr., Chicago, IL 60612. Phone: (312) 491-0846, ext. 213. Fax: (312) 491-0856. E-mail: andrei{at}integratedgenomics.com.

{dagger} Present address: Pharmacia Corp., Skokie, Ill.

{ddagger} Present address: Department of Human Genetics, Biological Sciences Division, University of Chicago, Chicago, Ill.

Journal of Bacteriology, December 2002, p. 6906-6917, Vol. 184, No. 24
0021-9193/02/$04.00+0     DOI: 10.1128/JB.184.24.6906-6917.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Gazzaniga, F., Stebbins, R., Chang, S. Z., McPeek, M. A., Brenner, C. (2009). Microbial NAD Metabolism: Lessons from Comparative Genomics. Microbiol. Mol. Biol. Rev. 73: 529-541 [Abstract] [Full Text]  
  • Sorci, L., Martynowski, D., Rodionov, D. A., Eyobo, Y., Zogaj, X., Klose, K. E., Nikolaev, E. V., Magni, G., Zhang, H., Osterman, A. L. (2009). Nicotinamide mononucleotide synthetase is the key enzyme for an alternative route of NAD biosynthesis in Francisella tularensis. Proc. Natl. Acad. Sci. USA 106: 3083-3088 [Abstract] [Full Text]  
  • Rodionov, D. A., Li, X., Rodionova, I. A., Yang, C., Sorci, L., Dervyn, E., Martynowski, D., Zhang, H., Gelfand, M. S., Osterman, A. L. (2008). Transcriptional regulation of NAD metabolism in bacteria: genomic reconstruction of NiaR (YrxA) regulon. Nucleic Acids Res 36: 2032-2046 [Abstract] [Full Text]  
  • Rodionov, D. A., De Ingeniis, J., Mancini, C., Cimadamore, F., Zhang, H., Osterman, A. L., Raffaelli, N. (2008). Transcriptional regulation of NAD metabolism in bacteria: NrtR family of Nudix-related regulators. Nucleic Acids Res 36: 2047-2059 [Abstract] [Full Text]  
  • Gerlach, G., Reidl, J. (2006). NAD+ utilization in pasteurellaceae: simplification of a complex pathway.. J. Bacteriol. 188: 6719-6727 [Full Text]  
  • Gerdes, S. Y., Kurnasov, O. V., Shatalin, K., Polanuyer, B., Sloutsky, R., Vonstein, V., Overbeek, R., Osterman, A. L. (2006). Comparative Genomics of NAD Biosynthesis in Cyanobacteria.. J. Bacteriol. 188: 3012-3023 [Abstract] [Full Text]  
  • Merdanovic, M., Sauer, E., Reidl, J. (2005). Coupling of NAD+ Biosynthesis and Nicotinamide Ribosyl Transport: Characterization of NadR Ribonucleotide Kinase Mutants of Haemophilus influenzae. J. Bacteriol. 187: 4410-4420 [Abstract] [Full Text]  
  • Grose, J. H., Bergthorsson, U., Xu, Y., Sterneckert, J., Khodaverdian, B., Roth, J. R. (2005). Assimilation of Nicotinamide Mononucleotide Requires Periplasmic AphA Phosphatase in Salmonella enterica. J. Bacteriol. 187: 4521-4530 [Abstract] [Full Text]  
  • Grose, J. H., Bergthorsson, U., Roth, J. R. (2005). Regulation of NAD Synthesis by the Trifunctional NadR Protein of Salmonella enterica. J. Bacteriol. 187: 2774-2782 [Abstract] [Full Text]  
  • Sauer, E., Merdanovic, M., Price Mortimer, A., Bringmann, G., Reidl, J. (2004). PnuC and the Utilization of the Nicotinamide Riboside Analog 3-Aminopyridine in Haemophilus influenzae. Antimicrob. Agents Chemother. 48: 4532-4541 [Abstract] [Full Text]  
  • Gil, R., Silva, F. J., Pereto, J., Moya, A. (2004). Determination of the Core of a Minimal Bacterial Gene Set. Microbiol. Mol. Biol. Rev. 68: 518-537 [Abstract] [Full Text]  
  • Stancek, M., Isaksson, L. A., Ryden-Aulin, M. (2003). fusB is an allele of nadD, encoding nicotinate mononucleotide adenylyltransferase in Escherichia coli. Microbiology 149: 2427-2433 [Abstract] [Full Text]  
  • Zhang, X., Kurnasov, O. V., Karthikeyan, S., Grishin, N. V., Osterman, A. L., Zhang, H. (2003). Structural Characterization of a Human Cytosolic NMN/NaMN Adenylyltransferase and Implication in Human NAD Biosynthesis. J. Biol. Chem. 278: 13503-13511 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»