Advertisement

N-Acetylneuraminic Acid Synthase (NANS)

  • Michael J. Betenbaugh
  • Bojiao Yin
  • Emily Blake
  • Linda Kristoffersen
  • Someet Narang
  • Karthik Viswanathan
Reference work entry

Abstract

The human gene NANS, also known as sialic acid (phosphate) synthase (SAS), encodes N-acetylneuraminic acid 9-phosphate synthase (Neu5Ac-9-P synthase), a cytosolic protein approximately 40 kDa in size and comprising 359 amino acids (Lawrence et al. 2000). Neu5Ac-9-P synthase plays a pivotal role in the primary synthesis of the most common sialic acid, N-acetylneuraminic acid (Neu5Ac, NeuNAc, or NeuAc). However, studies have shown that NANS can also contribute in humans to the enzymatic synthesis of other sialic acids including 2-keto-3-deoxy-d-glycero-d-galacto-nononic acid (KDN). Furthermore, as a critical step along the pathway towards the production of the principal sialylation substrates, CMP-Neu5Ac and CMP-Neu5Gc, NANS can also influence the sialylation of glycans in important ways.

Keywords

Sialic Acid Down Syndrome Neural Cell Adhesion Molecule Neisseria Meningitidis Antifreeze Protein 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

References

  1. Angata T, Nakata D, Matsuda T, Kitajima K, Troy FA 2nd (1999) Biosynthesis of KDN (2-keto-3-deoxy-D-glycero-D-galacto-nononic acid). Identification and characterization of a KDN-9-phosphate synthetase activity from trout testis. J Biol Chem 274:22949–22956PubMedCrossRefGoogle Scholar
  2. Annunziato PW, Wright LF, Vann WF, Silver RP (1995) Nucleotide sequence and genetic analysis of the neuD and neuB genes in region 2 of the polysialic acid gene cluster of Escherichia coli K1. J Bacteriol 177:312–319PubMedCentralPubMedGoogle Scholar
  3. Barry GT, Abbott V, Tsai T (1962) Relationship of colominic acid (poly N-acetylneuraminic acid) to bacteria which contain neuraminic acid. J Gen Microbiol 29:335–352PubMedCrossRefGoogle Scholar
  4. Blacklow RS, Warren L (1962) Biosynthesis of sialic acids by Neisseria meningitidis. J Biol Chem 237:3520–3526PubMedGoogle Scholar
  5. Chen H, Blume A, Zimmermann-Kordmann M, Reutter W, Hinderlich S (2002) Purification and characterization of N-acetylneuraminic acid-9-phosphate synthase from rat liver. Glycobiology 12:65–71PubMedCrossRefGoogle Scholar
  6. Cunningham BA, Hoffman S, Rutishauser U, Hemperly JJ, Edelman GM (1983) Molecular topography of the neural cell adhesion molecule N-CAM: surface orientation and location of sialic acid-rich and binding regions. Proc Natl Acad Sci USA 80:3116–3120PubMedCrossRefGoogle Scholar
  7. Frosch M, Weisgerber C, Meyer TF (1989) Molecular characterization and expression in Escherichia coli of the gene complex encoding the polysaccharide capsule of Neisseria meningitidis group B. Proc Natl Acad Sci USA 86:1669–1673PubMedCrossRefGoogle Scholar
  8. Fukuda M (1996) Possible roles of tumor-associated carbohydrate antigens. Cancer Res 56:2237–2244PubMedGoogle Scholar
  9. Ganguli S, Zapata G, Wallis T, Reid C, Boulnois G, Vann WF, Roberts IS (1994) Molecular cloning and analysis of genes for sialic acid synthesis in Neisseria meningitidis group B and purification of the meningococcal CMP-NeuNAc synthetase enzyme. J Bacteriol 176:4583–4589PubMedCentralPubMedGoogle Scholar
  10. Go S, Sato C, Yin J, Kannagi R, Kitajima K (2007) Hypoxia-enhanced expression of free deaminoneuraminic acid in human cancer cells. Biochem Biophys Res Commun 357:537–542PubMedCrossRefGoogle Scholar
  11. Gorelik E, Galili U, Raz A (2001) On the role of cell surface carbohydrates and their binding proteins (lectins) in tumor metastasis. Cancer Metastasis Rev 20:245–277PubMedCrossRefGoogle Scholar
  12. Granell AE, Palter KB, Akan I, Aich U, Yarema KJ, Betenbaugh MJ, Thornhill WB, Recio-Pinto E (2011) DmSAS is required for sialic acid biosynthesis in cultured Drosophila third instar larvae CNS neurons. ACS Chem Biol 6:1287–1295PubMedCrossRefGoogle Scholar
  13. Grossmann M, Wong R, Teh NG, Tropea JE, East-Palmer J, Weintraub BD, Szkudlinski MW (1997) Expression of biologically active human thyrotropin (hTSH) in a baculovirus system: effect of insect cell glycosylation on hTSH activity in vitro and in vivo. Endocrinology 138:92–100PubMedGoogle Scholar
  14. Gulesserian T, Engidawork E, Fountoulakis M, Lubec G (2007) Manifold decrease of sialic acid synthase in fetal down syndrome brain. Amino Acids 32:141–144PubMedCrossRefGoogle Scholar
  15. Gunawan J, Simard D, Gilbert M, Lovering AL, Wakarchuk WW, Tanner ME, Strynadka NC (2005) Structural and mechanistic analysis of sialic acid synthase NeuB from Neisseria meningitidis in complex with Mn2+, phosphoenolpyruvate, and N-acetylmannosaminitol. J Biol Chem 280:3555–3563PubMedCrossRefGoogle Scholar
  16. Hamada T et al (2006) Solution structure of the antifreeze-like domain of human sialic acid synthase. Protein Sci 15:1010–1016PubMedCrossRefGoogle Scholar
  17. Hao J, Balagurumoorthy P, Sarilla S, Sundaramoorthy M (2005) Cloning, expression, and characterization of sialic acid synthases. Biochem Biophys Res Commun 338:1507–1514PubMedCrossRefGoogle Scholar
  18. Hao J, Vann WF, Hinderlich S, Sundaramoorthy M (2006) Elimination of 2-keto-3-deoxy-D-glycero-D-galacto-nonulosonic acid 9-phosphate synthase activity from human N-acetylneuraminic acid 9-phosphate synthase by a single mutation. Biochem J 397:195–201PubMedCrossRefGoogle Scholar
  19. Hara S, Yamaguchi M, Takemori Y, Furuhata K, Ogura H, Nakamura M (1989) Determination of mono-O-acetylated N-acetylneuraminic acids in human and rat sera by fluorometric high-performance liquid chromatography. Anal Biochem 179:162–166PubMedCrossRefGoogle Scholar
  20. Hoffman S, Edelman GM (1983) Kinetics of homophilic binding by embryonic and adult forms of the neural cell adhesion molecule. Proc Natl Acad Sci USA 80:5762–5766PubMedCrossRefGoogle Scholar
  21. Huang HH, Liao HK, Chen YJ, Hwang TS, Lin YH, Lin CH (2005) Structural characterization of sialic acid synthase by electrospray mass spectrometry – a tetrameric enzyme composed of dimeric dimers. J Am Soc Mass Spectrom 16:324–332PubMedCrossRefGoogle Scholar
  22. Inoue S, Lin SL, Chang T, Wu SH, Yao CW, Chu TY, Troy FA 2nd, Inoue Y (1998) Identification of free deaminated sialic acid (2-keto-3-deoxy-D-glycero-D-galacto-nononic acid) in human red blood cells and its elevated expression in fetal cord red blood cells and ovarian cancer cells. J Biol Chem 273:27199–27204PubMedCrossRefGoogle Scholar
  23. Jourdian GW, Swanson AL, Watson D, Roseman S (1964) Isolation of sialic acid 9-Phosphatase from human erythrocytes. J Biol Chem 239:PC2714–PC2716PubMedGoogle Scholar
  24. Kim K, Lawrence SM, Park J, Pitts L, Vann WF, Betenbaugh MJ, Palter KB (2002) Expression of a functional Drosophila melanogaster N-acetylneuraminic acid (Neu5Ac) phosphate synthase gene: evidence for endogenous sialic acid biosynthetic ability in insects. Glycobiology 12:73–83PubMedCrossRefGoogle Scholar
  25. Komaki E, Ohta Y, Tsukada Y (1997) Purification and characterization of N-acetylneuraminate synthase from Escherichia coli K1-M12. Biosci Biotechnol Biochem 61:2046–2050PubMedCrossRefGoogle Scholar
  26. Kundig W, Ghosh S, Roseman S (1966) The sialic acids. VII. N-acyl-D-mannosamine kinase from rat liver. J Biol Chem 241:5619–5626PubMedGoogle Scholar
  27. Lawrence SM, Huddleston KA, Pitts LR, Nguyen N, Lee YC, Vann WF, Coleman TA, Betenbaugh MJ (2000) Cloning and expression of the human N-acetylneuraminic acid phosphate synthase gene with 2-keto-3-deoxy-D-glycero- D-galacto-nononic acid biosynthetic ability. J Biol Chem 275:17869–17877PubMedCrossRefGoogle Scholar
  28. Linton D, Karlyshev AV, Hitchen PG, Morris HR, Dell A, Gregson NA, Wren BW (2000) Multiple N-acetyl neuraminic acid synthetase (neuB) genes in Campylobacter jejuni: identification and characterization of the gene involved in sialylation of lipo-oligosaccharide. Mol Microbiol 35:1120–1134PubMedCrossRefGoogle Scholar
  29. Nakata D, Close BE, Colley KJ, Matsuda T, Kitajima K (2000) Molecular cloning and expression of the mouse N-acetylneuraminic acid 9-phosphate synthase which does not have deaminoneuraminic acid (KDN) 9-phosphate synthase activity. Biochem Biophys Res Commun 273:642–648PubMedCrossRefGoogle Scholar
  30. Preston A, Mandrell RE, Gibson BW, Apicella MA (1996) The lipooligosaccharides of pathogenic gram-negative bacteria. Crit Rev Microbiol 22:139–180PubMedCrossRefGoogle Scholar
  31. Reaves ML, Lopez LC, Daskalova SM (2008) Replacement of the antifreeze-like domain of human N-acetylneuraminic acid phosphate synthase with the mouse antifreeze-like domain impacts both N-acetylneuraminic acid 9-phosphate synthase and 2-keto-3-deoxy-D-glycero-D-galacto-nonulosonic acid 9-phosphate synthase activities. BMB Rep 41:72–78PubMedCrossRefGoogle Scholar
  32. Roseman S, Jourdian GW, Watson D, Rood R (1961) Enzymatic synthesis of sialic acid 9-phosphates. Proc Natl Acad Sci USA 47:958–961PubMedCrossRefGoogle Scholar
  33. Rutishauser U (1998) Polysialic acid at the cell surface: biophysics in service of cell interactions and tissue plasticity. J Cell Biochem 70:304–312PubMedCrossRefGoogle Scholar
  34. Silver RP, Vann WF, Aaronson W (1984) Genetic and molecular analyses of Escherichia coli K1 antigen genes. J Bacteriol 157:568–575PubMedCentralPubMedGoogle Scholar
  35. Suzuki Y (2005) Sialobiology of influenza: molecular mechanism of host range variation of influenza viruses. Biol Pharm Bull 28:399–408PubMedCrossRefGoogle Scholar
  36. Takano R, Muchmore E, Dennis JW (1994) Sialylation and malignant potential in tumour cell glycosylation mutants. Glycobiology 4:665–674PubMedCrossRefGoogle Scholar
  37. Traving C, Schauer R (1998) Structure, function and metabolism of sialic acids. Cell Mol Life Sci 54:1330–1349PubMedCrossRefGoogle Scholar
  38. Vann WF, Tavarez JJ, Crowley J, Vimr E, Silver RP (1997) Purification and characterization of the Escherichia coli K1 neuB gene product N-acetylneuraminic acid synthetase. Glycobiology 7:697–701PubMedCrossRefGoogle Scholar
  39. Varki A (1997) Sialic acids as ligands in recognition phenomena. FASEB J 11:248–255PubMedGoogle Scholar
  40. Varki A (2007) Glycan-based interactions involving vertebrate sialic-acid-recognizing proteins. Nature 446:1023–1029PubMedCrossRefGoogle Scholar
  41. Varki A, Angata T (2006) Siglecs – the major subfamily of I-type lectins. Glycobiology 16:1R–27RPubMedCrossRefGoogle Scholar
  42. Vimr ER, Kalivoda KA, Deszo EL, Steenbergen SM (2004) Diversity of microbial sialic acid metabolism. Microbiol Mol Biol Rev 68:132–153PubMedCentralPubMedCrossRefGoogle Scholar
  43. Warren L (1959) The thiobarbituric acid assay of sialic acids. J Biol Chem 234:1971–1975PubMedGoogle Scholar
  44. Watson DR, Jourdian GW, Roseman S (1966) The sialic acids. 8. Sialic acid 9-phosphate synthetase. J Biol Chem 241:5627–5636PubMedGoogle Scholar
  45. Wierenga RK (2001) The TIM-barrel fold: a versatile framework for efficient enzymes. FEBS Lett 492:193–198PubMedCrossRefGoogle Scholar
  46. Yabu M, Korekane H, Hatano K, Kaneda Y, Nonomura N, Sato C, Kitajima K, Miyamoto Y (2012) Occurrence of free deaminoneuraminic acid (KDN)-containing complex-type N-glycans in human prostate cancers. Glycobiology 23:634–642PubMedCrossRefGoogle Scholar

Copyright information

© Springer Japan 2014

Authors and Affiliations

  • Michael J. Betenbaugh
    • 1
  • Bojiao Yin
    • 1
  • Emily Blake
    • 1
  • Linda Kristoffersen
    • 1
  • Someet Narang
    • 2
  • Karthik Viswanathan
    • 3
  1. 1.Department of Chemical and Biomolecular EngineeringJohns Hopkins UniversityBaltimoreUSA
  2. 2.MedImmuneGaithersburgUSA
  3. 3.Department of Biological EngineeringMassachusetts Institute of TechnologyCambridgeUSA

Personalised recommendations