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Cytidine Monophosphate N-Acetylneuraminic Acid Synthetase (CMAS)

  • Birgit Weinhold
  • Rita Gerardy-Schahn
  • Anja Münster-Kühnel
Reference work entry

Abstract

The cytidine monophosphate N-acetylneuraminic acid synthetase (CMAS) catalyzes the activation of the nine-carbon amino sugar N-acetylneuraminic acid (NeuAc) and other sialic acid (Sia) derivatives to the sugar nucleotide cytidine monophosphate N-acetylneuraminic acid (CMP-NeuAc or CMP-Sia) (Kean 1991) by the following reaction:
$$ \mathrm{CTP}+\mathrm{NeuAc}\to \mathrm{CMP}-\mathrm{NeuAc}+\mathrm{PPi} $$

Keywords

Rainbow Trout Sialic Acid Nuclear Import Neisseria Meningitidis Purine Nucleoside Phosphorylase 
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. Allen KN, Dunaway-Mariano D (2004) Phosphoryl group transfer: evolution of a catalytic scaffold. Trends Biochem Sci 29:495–503PubMedCrossRefGoogle Scholar
  2. Angata T, Varki A (2002) Chemical diversity in the sialic acids and related alpha-keto acids: an evolutionary perspective. Chem Rev 102:439–469PubMedCrossRefGoogle Scholar
  3. Burroughs AM, Allen KN, Dunaway-Mariano D, Aravind L (2006) Evolutionary genomics of the HAD superfamily: understanding the structural adaptations and catalytic diversity in a superfamily of phosphoesterases and allied enzymes. J Mol Biol 361:1003–1034PubMedCrossRefGoogle Scholar
  4. Cohen M, Varki A (2010) The sialome–far more than the sum of its parts. OMICS 14:455–464PubMedCrossRefGoogle Scholar
  5. Comb DG, Watson DR, Roseman S (1966) The sialic acids. IX. Isolation of cytidine 5′-monophospho-N-acetylneuraminic acid from Escherichia coli K-235. J Biol Chem 241:5637–5642PubMedGoogle Scholar
  6. Comb DG, Shimizu F, Roseman S (1959) Isolation of cytidine 5′-monophospho-N-acetylneuraminic acid. J Am Chem Soc 81:5513–5514CrossRefGoogle Scholar
  7. Emig S, Schmalz D, Shakibaei M, Buchner K (1995) The nuclear pore complex protein p62 is one of several sialic acid-containing proteins of the nuclear envelope. J Biol Chem 270:13787–13793PubMedCrossRefGoogle Scholar
  8. Fujita A, Sato C, Kitajima K (2007) Identification of the nuclear export signals that regulate the intracellular localization of the mouse CMP-sialic acid synthetase. Biochem Biophys Res Commun 355:174–180PubMedCrossRefGoogle Scholar
  9. Fujita A, Sato C, Münster-Kühnel AK, Gerardy-Schahn R, Kitajima K (2005) Development of a simple and efficient method for assaying cytidine monophosphate sialic acid synthetase activity using an enzymatic reduced nicotinamide adenine dinucleotide/oxidized nicotinamide adenine dinucleotide converting system. Anal Biochem 337:12–21PubMedCrossRefGoogle Scholar
  10. Ghalambor MA, Heath EC (1966) The biosynthesis of cell wall lipopolysaccharide in Escherichia coli. IV. Purification and properties of cytidine monophosphate 3-deoxy-d- manno-octulosonate synthetase. J Biol Chem 241:3216–3221PubMedGoogle Scholar
  11. Gross HJ, Brossmer R (1987) N-Acetyl-4-deoxy-D-neuraminic Acid is activated and transferred on to Asialoglycoprotein. Glycoconj J 4:145–156CrossRefGoogle Scholar
  12. Gross HJ, Bunsch A, Paulson JC, Brossmer R (1987) Activation and transfer of novel synthetic 9-substituted sialic acids. Eur J Biochem 168:595–602PubMedCrossRefGoogle Scholar
  13. Haft RF, Wessels MR (1994) Characterization of CMP-N-acetylneuraminic acid synthetase of group B streptococci. J Bacteriol 176:7372–7374PubMedCentralPubMedGoogle Scholar
  14. Hinderlich S, Stäsche R, Zeitler R, Reutter W (1997) A bifunctional enzyme catalyzes the first two steps in N-acetylneuraminic acid biosynthesis of rat liver. Purification and characterization of UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase. J Biol Chem 272:24313–24318PubMedCrossRefGoogle Scholar
  15. Horsfall LE, Nelson A, Berry A (2010) Identification and characterization of important residues in the catalytic mechanism of CMP-Neu5Ac synthetase from Neisseria meningitidis. FEBS J 277:2779–2790PubMedCentralPubMedCrossRefGoogle Scholar
  16. Kean EL (1969) Sialic acid activating enzyme in ocular tissue. Exp Eye Res 8:44–54PubMedCrossRefGoogle Scholar
  17. Kean EL (1970) Nuclear cytidine 5′-monophosphosialic acid synthetase. J Biol Chem 245:2301–2308PubMedGoogle Scholar
  18. Kean EL (1991) Sialic acid activation. Glycobiology 1:441–447PubMedCrossRefGoogle Scholar
  19. Kean EL, Bighouse KJ (1974) Cytidine 5′-monophosphosialic acid hydrolase. Subcellular location and properties. J Biol Chem 249:7813–7823PubMedGoogle Scholar
  20. Kean EL, Münster-Kühnel AK, Gerardy-Schahn R (2004) CMP-sialic acid synthetase of the nucleus. Biochimica et Biophysica Acta-General Subjects 1673:56–65CrossRefGoogle Scholar
  21. Kean EL, Roseman S (1966) The sialic acids. X. Purification and properties of cytidine 5′-monophosphosialic acid synthetase. J Biol Chem 241:5643–5650PubMedGoogle Scholar
  22. Krapp S, Münster-Kühnel AK, Kaiser JT, Huber R, Tiralongo J, Gerardy-Schahn R, Jacob U (2003) The crystal structure of murine CMP-5-N-acetylneuraminic acid synthetase. J Mol Biol 334:625–637PubMedCrossRefGoogle Scholar
  23. Lawrence SM, Huddleston KA, Tomiya N, Nguyen N, Lee YC, Vann WF, Coleman TA, Betenbaugh MJ (2001) Cloning and expression of human sialic acid pathway genes to generate CMP-sialic acids in insect cells. Glycoconj J 18:205–213PubMedCrossRefGoogle Scholar
  24. Lewis AL, Cao H, Patel SK, Diaz S, Ryan W, Carlin AF, Thon V, Lewis WG, Varki A, Chen X, Nizet V (2007) NeuA sialic acid O-acetylesterase activity modulates O-acetylation of capsular polysaccharide in group B streptococcus. J Biol Chem 282:27562–27571PubMedCentralPubMedCrossRefGoogle Scholar
  25. Mizanur RM, Pohl NL (2007) Cloning and characterization of a heat-stable CMP-N-acylneuraminic acid synthetase from clostridium thermocellum. Appl Microbiol Biotechnol 76:827–834PubMedCrossRefGoogle Scholar
  26. Mizanur RM, Pohl NL (2008) Bacterial CMP-sialic acid synthetases: production, properties, and applications. Appl Microbiol Biotechnol 80:757–765PubMedCrossRefGoogle Scholar
  27. Mosimann SC, Gilbert M, Dombroswki D, To R, Wakarchuk W, Strynadka NC (2001) Structure of a sialic acid-activating synthetase, CMP-acylneuraminate synthetase in the presence and absence of CDP. J Biol Chem 276:8190–8196PubMedCrossRefGoogle Scholar
  28. Münster AK, Eckhardt M, Potvin B, Mühlenhoff M, Stanley P, Gerardy-Schahn R (1998) Mammalian cytidine 5′-monophosphate N-acetylneuraminic acid synthetase: a nuclear protein with evolutionarily conserved structural motifs. Proc Natl Acad Sci U S A 95:9140–9145PubMedCentralPubMedCrossRefGoogle Scholar
  29. Münster AK, Weinhold B, Gotza B, Mühlenhoff M, Frosch M, Gerardy-Schahn R (2002) Nuclear localization signal of murine CMP-Neu5Ac synthetase includes residues required for both nuclear targeting and enzymatic activity. J Biol Chem 277:19688–19696PubMedCrossRefGoogle Scholar
  30. Münster-Kühnel AK, Tiralongo J, Krapp S, Weinhold B, Ritz-Sedlacek V, Jacob U, Gerardy-Schahn R (2004) Structure and function of vertebrate CMP-sialic acid synthetases. Glycobiology 14:43R–51RPubMedCrossRefGoogle Scholar
  31. Nakata D, Münster AK, Gerardy-Schahn R, Aoki N, Matsuda T, Kitajima K (2001) Molecular cloning of a unique CMP-sialic acid synthetase that effectively utilizes both deaminoneuraminic acid (KDN) and N- acetylneuraminic acid (Neu5Ac) as substrates. Glycobiology 11:685–692PubMedCrossRefGoogle Scholar
  32. Oschlies M, Dickmanns A, Haselhorst T, Schaper W, Stummeyer K, Tiralongo J, Weinhold B, Gerardy-Schahn R, von Itzstein M, Ficner R, Münster-Kühnel AK (2009) A C-terminal phosphatase module conserved in vertebrate CMP-sialic acid synthetases provides a tetramerization interface for the physiologically active enzyme. J Mol Biol 393:83–97PubMedCrossRefGoogle Scholar
  33. Potvin B, Raju TS, Stanley P (1995) Lec32 is a new mutation in Chinese hamster ovary cells that essentially abrogates CMP-N-acetylneuraminic acid synthetase activity. J Biol Chem 270:30415–30421PubMedCrossRefGoogle Scholar
  34. Richard M, Martin A, Louisot P (1975) Evidence for glycosyl-transferases in rat liver nuclei. Biochem Biophys Res Commun 64:109–114PubMedCrossRefGoogle Scholar
  35. Rodriguez-Aparicio LB, Luengo JM, Gonzalez-Clemente C, Reglero A (1992) Purification and characterization of the nuclear cytidine 5′-monophosphate N-acetylneuraminic acid synthetase from rat liver. J Biol Chem 267:9257–9263PubMedGoogle Scholar
  36. Roseman S (1962) Enzymatic synthesis of cytidine 5′-mono-phospho-sialic acids. Proc Natl Acad Sci U S A 48:437–441PubMedCentralPubMedCrossRefGoogle Scholar
  37. Schaper W, Bentrop J, Ustinova J, Blume L, Kats E, Tiralongo J, Weinhold B, Bastmeyer M, Münster-Kühnel AK (2012) Identification and biochemical characterization of two functional CMP-sialic acid synthetases in Danio rerio. J Biol Chem 287:13239–13248PubMedCrossRefGoogle Scholar
  38. Schauer R, Haverkamp J, Ehrlich K (1980) Isolation and characterization of acylneuraminate cytidylyltransferase from frog liver. Hoppe Seylers Z Physiol Chem 361:641–648PubMedCrossRefGoogle Scholar
  39. Schwarzkopf M, Knobeloch KP, Rohde E, Hinderlich S, Wiechens N, Lucka L, Horak I, Reutter W, Horstkorte R (2002) Sialylation is essential for early development in mice. Proc Natl Acad Sci U S A 99:5267–5270PubMedCentralPubMedCrossRefGoogle Scholar
  40. Shoyab M, Bachhawat BK (1967) Age dependent changes in the level of cytidine 5′-monophospho-N-acetyl neuraminic acid synthesizing and degrading enzymes and bound sialic acid in rat liver. Indian J Biochem 4:142–145PubMedGoogle Scholar
  41. Shoyab M, Pattabiraman TN, Bachhawat BK (1964) Purification and properties of the CMP-N-acetylneuraminic acid synthesizing enzyme from sheep brain. J Neurochem 11:639–646PubMedCrossRefGoogle Scholar
  42. Steenbergen SM, Lee YC, Vann WF, Vionnet J, Wright LF, Vimr ER (2006) Separate pathways for O acetylation of polymeric and monomeric sialic acids and identification of sialyl O-acetyl esterase in Escherichia coli K1. J Bacteriol 188:6195–6206PubMedCentralPubMedCrossRefGoogle Scholar
  43. Svennerholm L (1956) The quantitative estimation of cerebrosides in nervous tissue. J Neurochem 1:42–53PubMedCrossRefGoogle Scholar
  44. Terada T, Kitajima K, Inoue S, Koppert K, Brossmer R, Inoue Y (1996) Substrate specificity of rainbow trout testis CMP-3-deoxy-D-glycero-D-galacto-nonulosonic acid (CMP-Kdn) synthetase: kinetic studies of the reaction of natural and synthetic analogues of nonulosonic acid catalyzed by CMP-Kdn synthetase. Eur J Biochem 236:852–855PubMedCrossRefGoogle Scholar
  45. Terada T, Kitazume S, Kitajima K, Inoue S, Ito F, Troy FA, Inoue Y (1993) Synthesis of CMP-deaminoneuraminic acid (CMP-KDN) using the CTP: CMP-3- deoxynonulosonate cytidylyltransferase from rainbow trout testis. Identification and characterization of a CMP-KDN synthetase. J Biol Chem 268:2640–2648PubMedGoogle Scholar
  46. Tiralongo J, Fujita A, Sato C, Kitajima K, Lehmann F, Oschlies M, Gerardy-Schahn R, Münster-Kühnel AK (2007) The rainbow trout CMP-sialic acid synthetase utilises a nuclear localization signal different from that identified in the mouse enzyme. Glycobiology 17:945–954PubMedCrossRefGoogle Scholar
  47. Van den Eijnden DH, Meems L, Roukema PA (1972) The regional distribution of cytidine 5′-monophospho-N-acetyl-neuraminic acid synthetase in calf brain. J Neurochem 19:1649–1658PubMedCrossRefGoogle Scholar
  48. van Dijk W, Ferwerda W, Van den Eijnden DH (1973) Subcellular and regional distribution of CMP-N-acetylneuraminic acid synthetase in the calf kidney. Biochim Biophys Acta 315:162–175PubMedCrossRefGoogle Scholar
  49. Vann WF, Silver RP, Abeijon C, Chang K, Aaronson W, Sutton A, Finn CW, Lindner W, Kotsatos M (1987) Purification, properties, and genetic location of Escherichia coli cytidine 5′-monophosphate N-acetylneuraminic acid synthetase. J Biol Chem 262:17556–17562PubMedGoogle Scholar
  50. Varki NM, Varki A (2007) Diversity in cell surface sialic acid presentations: implications for biology and disease. Lab Invest 87:851–857PubMedCrossRefGoogle Scholar
  51. Vimr ER, Aaronson W, Silver RP (1989) Genetic analysis of chromosomal mutations in the polysialic acid gene cluster of Escherichia coli K1. J Bacteriol 171:1106–1117PubMedCentralPubMedGoogle Scholar
  52. Vionnet J, Concepcion N, Warner T, Zapata G, Hanover J, Vann WF (1999) Purification of CMP-N-acetylneuraminic acid synthetase from bovine anterior pituitary glands. Glycobiology 9:481–487PubMedCrossRefGoogle Scholar
  53. Viswanathan K, Tomiya N, Park J, Singh S, Lee YC, Palter K, Betenbaugh MJ (2006) Expression of a functional drosophila melanogaster CMP-sialic acid synthetase. Differential localization of the drosophila and human enzymes. J Biol Chem 281:15929–15940PubMedCrossRefGoogle Scholar
  54. Warren L (1959) The thiobarbituric acid assay of sialic acids. J Biol Chem 234:1971–1975PubMedGoogle Scholar
  55. Warren L, Blacklow RS (1962) The biosynthesis of cytidine 5′-monophospho-n-acetylneuraminic acid by an enzyme from Neisseria meningitidis. J Biol Chem 237:3527–3534PubMedGoogle Scholar
  56. Weinhold B, Sellmeier M, Schaper W, Blume L, Philippens B, Kats E, Bernard U, Galuska SP, Geyer H, Geyer R, Worthmann K, Schiffer M, Groos S, Gerardy-Schahn R, Münster-Kühnel AK (2012) Deficits in sialylation impair podocyte maturation. J Am Soc Nephrol 23:1319–1328PubMedCrossRefGoogle Scholar
  57. Yu H, Ryan W, Yu H, Chen X (2006) Characterization of a bifunctional cytidine 5′-monophosphate N-acetylneuraminic acid synthetase cloned from Streptococcus agalactiae. Biotechnol Lett 28:107–113PubMedCrossRefGoogle Scholar
  58. Zapata G, Vann WF, Aaronson W, Lewis MS, Moos M (1989) Sequence of the cloned Escherichia coli K1 CMP-N-acetylneuraminic acid synthetase gene. J Biol Chem 264:14769–14774PubMedGoogle Scholar

Copyright information

© Springer Japan 2014

Authors and Affiliations

  • Birgit Weinhold
    • 1
  • Rita Gerardy-Schahn
    • 1
  • Anja Münster-Kühnel
    • 1
  1. 1.Institute for Cellular ChemistryHannover Medical SchoolHannoverGermany

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