Enzymology of Influenza Virus Sialidase

Chapter
Part of the Milestones in Drug Therapy book series (MDT)

Abstract

Influenza virus sialidase plays a key role in the infectious lifecycle of the virus. This chapter provides a discussion of the tools, such as linear free energy relationships and kinetic isotope effects, used in exploring enzyme mechanisms and an introduction to mechanistic aspects, including transition state analysis and whether the intermediate that follows the glycosylation TS, in retaining glycosidases, is an oxacarbenium ion or is covalently linked to the enzyme. A general discussion of microbial sialidase catalysis is provided, as well as an overview of the catalytic mechanism of influenza virus sialidases.

References

  1. 1.
    Saito M, Yu RK (1995) Biochemistry and function of sialidases. In: Rosenberg A (ed) Biology of the sialic acids. Plenum Press, New York, pp 261–313Google Scholar
  2. 2.
    Nelson J, Couceiro SS, Paulson JC, Baum LG (1993) Influenza-virus strains selectively recognize sialyloligosaccharides on human respiratory epithelium – the role of the host-cell in selection of hemagglutinin receptor specificity. Virus Res 29:155–165CrossRefGoogle Scholar
  3. 3.
    Wilson JC, von Itzstein M (2003) Recent strategies in the search for new anti-influenza therapies. Curr Drug Targets 4:389–408PubMedCrossRefGoogle Scholar
  4. 4.
    de Barros JF, Alviano DS, da Silva MH, Wigg MD, Alviano CS, Schauer R, Couceiro J (2003) Characterization of sialidase from an influenza A (H3N2) virus strain: kinetic parameters and substrate specificity. Intervirology 46:199–206CrossRefGoogle Scholar
  5. 5.
    Wilson JC, Angus DI, von Itzstein M (1995) 1H NMR evidence that Salmonella typhimurium sialidase hydrolyzes sialosides with overall retention of configuration. J Am Chem Soc 117:4214–4217CrossRefGoogle Scholar
  6. 6.
    Davies G, Sinnott ML, Withers SG (1998) Glycosyl Transfer. In: Sinnott ML (ed) Comprehensive biological catalysis. Academic, San Diego, CA, pp 119–209Google Scholar
  7. 7.
    Friebolin H, Supp M, Brossmer R, Keilich G, Ziegler D (1980) 1 H-NMR investigations on the mutarotation of N-acetyl-D-neuraminic acid. Angew Chem Int Ed Engl 19:208–209CrossRefGoogle Scholar
  8. 8.
    Friebolin H, Kunzelmann P, Supp M, Brossmer R, Keilich G, Ziegler D (1981) 1 H-NMR-spekroskopische untersuchungen zur mutarotation der N-acetyl-D-neuraminsäure - pH-abhängigkeit der mutarotationsgeschwindigkeit. Tetrahedron Lett 22:1383–1386CrossRefGoogle Scholar
  9. 9.
    Klepach T, Carmichael I, Serianni AS (2008) 13C-Labeled N-acetyl-neuraminic acid in aqueous solution: Detection and quantification of acyclic keto, keto hydrate, and enol forms by 13C NMR spectroscopy. J Am Chem Soc 130:11892–11900PubMedCrossRefGoogle Scholar
  10. 10.
    Stummeyer K, Dickmanns A, Muhlenhoff M, Gerardy-Schahn R, Ficner R (2005) Crystal structure of the polysialic acid-degrading endosialidase of bacteriophage K1F. Nat Struct Mol Biol 12:90–96PubMedCrossRefGoogle Scholar
  11. 11.
    Pelkonen S, Pelkonen J, Finne J (1989) Common cleavage pattern of polysialic acid by bacteriophage endosialidases of different properties and origins. J Virol 63:4409–4416PubMedGoogle Scholar
  12. 12.
    Morley TJ, Willis LM, Whitfield C, Wakarchuk WW, Withers SG (2009) A new sialidase mechanism: Bacteriophage K1F endosialidase is an inverting glycosidase. J Biol Chem 284:17404–17410PubMedCrossRefGoogle Scholar
  13. 13.
    Schauer R (1985) Sialic acids and their role as biological masks. Trend Biochem Sci 10:357–360CrossRefGoogle Scholar
  14. 14.
    Miyagi T, Kato K, Ueno S, Wada T (2004) Aberrant expression of sialidase in cancer. Trends Glycosci Glycotechnol 16:371–381CrossRefGoogle Scholar
  15. 15.
    Corfield T (1992) Bacterial sialidases: roles in pathogenicity and nutrition. Glycobiology 2:509–521PubMedCrossRefGoogle Scholar
  16. 16.
    Taylor G (1996) Sialidases: Structures, biological significance and therapeutic potential. Curr Opin Struct Biol 6:830–837PubMedCrossRefGoogle Scholar
  17. 17.
    Klenk H-D, Rott R (1988) The molecular biology of influenza virus pathogenicity. In: Maramorosch K, Murphy FA, Shatkin AJ (eds) Advances in virus research. Academic, New York, pp 247–281Google Scholar
  18. 18.
    Palese P, Tobita K, Ueda M, Compans RW (1974) Characterization of temperature sensitive influenza virus mutants defective in neuraminidase. Virology 61:397–410PubMedCrossRefGoogle Scholar
  19. 19.
    von Itzstein M (2007) The war against influenza: discovery and development of sialidase inhibitors. Nat Rev Drug Discov 6:967–974CrossRefGoogle Scholar
  20. 20.
    Islam T, von Itzstein M (2007) Anti-influenza drug discovery: Are we ready for the next pandemic? Adv Carbohydr Chem Biochem 61:293–352PubMedCrossRefGoogle Scholar
  21. 21.
    Michaelis L, Menten ML (1913) Die kinetik der invertinwirkung. Biochem Zeit 49:333–369Google Scholar
  22. 22.
    Fersht A (1985) Enzyme structure and mechanism, 2nd edn. W.H. Freeman, New YorkGoogle Scholar
  23. 23.
    Hudson CS (1907) The catalysis by acids and bases of the mutarotation of glucose. J Am Chem Soc 29:1571–1576CrossRefGoogle Scholar
  24. 24.
    Lewis BE, Choytun N, Schramm VL, Bennet AJ (2006) Transition states for glucopyranose interconversion. J Am Chem Soc 128:5049–5058PubMedCrossRefGoogle Scholar
  25. 25.
    Severi E, Muller A, Potts JR, Leech A, Williamson D, Wilson KS, Thomas GH (2008) Sialic acid mutarotation is catalyzed by the Escherichia coli beta-propeller protein YjhT. J Biol Chem 283:4841–4849PubMedCrossRefGoogle Scholar
  26. 26.
    Albery WJ, Knowles JR (1976) Evolution of enzyme function and development of catalytic efficiency. Biochemistry 15:5631–5640PubMedCrossRefGoogle Scholar
  27. 27.
    Sinnott M (1998) Comprehensive biological catalysis: A mechanistic reference. Academic, San Diego,CAGoogle Scholar
  28. 28.
    Sinnott ML (2007) Carbohydrate chemistry and biochemistry: structure and mechanism. RSC Publishing, CambridgeGoogle Scholar
  29. 29.
    Ashwell M, Guo X, Sinnott ML (1992) Pathways for the hydrolysis of glycosides of N-acetylneuraminic acid. J Am Chem Soc 114:10158–10166CrossRefGoogle Scholar
  30. 30.
    Dookhun V, Bennet AJ (2005) Unexpected stability of aryl β-N-acetylneuraminides in neutral solution: Biological implications for sialyl transfer reactions. J Am Chem Soc 127:7458–7465PubMedCrossRefGoogle Scholar
  31. 31.
    Chou DTH, Watson JN, Scholte AA, Borgford TJ, Bennet AJ (2000) Effect of neutral pyridine leaving groups on the mechanisms of influenza type A viral sialidase-catalyzed and the spontaneous hydrolysis reactions of α-D-N-acetylneuraminides. J Am Chem Soc 122:8357–8364CrossRefGoogle Scholar
  32. 32.
    Melander LCS, Saunders WHJ (1980) Reaction rates of isotopic molecules. Wiley, New YorkGoogle Scholar
  33. 33.
    Kohen A, Limbach H-H (2006) Isotope effects in chemistry and biology. Taylor & Francis, Boca Raton, FLGoogle Scholar
  34. 34.
    Namchuk MN, McCarter JD, Becalski A, Andrews T, Withers SG (2000) The role of sugar substituents in glycoside hydrolysis. J Am Chem Soc 122:1270–1277CrossRefGoogle Scholar
  35. 35.
    Knoll TL, Bennet AJ (2004) Aqueous methanolysis of an α-D-N-acetylneuraminyl pyridinium zwitterion: Solvolysis occurs with no intramolecular participation of the anomeric carboxylate group. J Phys Org Chem 17:478–482CrossRefGoogle Scholar
  36. 36.
    Horenstein BA, Bruner M (1996) Acid-catalyzed solvolysis of CMP-N-acetyl neuraminate: evidence for a sialyl cation with a finite lifetime. J Am Chem Soc 118:10371–10379CrossRefGoogle Scholar
  37. 37.
    Horenstein BA, Bruner M (1998) The N-acetyl neuraminyl oxecarbenium ion is an intermediate in the presence of anionic nucleophiles. J Am Chem Soc 120:1357–1362CrossRefGoogle Scholar
  38. 38.
    Amyes TL, Jencks WP (1989) Lifetimes of oxocarbenium ions in aqueous solution from common ion inhibition of the solvolysis of α-azido ethers by added azide ion. J Am Chem Soc 111:7888–7900CrossRefGoogle Scholar
  39. 39.
    Huang X, Surry C, Hiebert T, Bennet AJ (1995) The hydrolysis of 2-deoxy-β-D-glucopyranosyl pyridinium salts. J Am Chem Soc 117:10614–10621CrossRefGoogle Scholar
  40. 40.
    Vimr ER (1994) Microbial sialidases: does bigger always mean better? Trends Microbiol 2:271–277PubMedCrossRefGoogle Scholar
  41. 41.
    Henrissat B, Bairoch A (1996) Updating the sequence-based classification of glycosyl hydrolases. Biochem J 316:695–696PubMedGoogle Scholar
  42. 42.
    Lentz MR, Webster RG, Air GM (1987) Site-directed mutation of the active site of influenza neuraminidase and implications for the catalytic mechanism. Biochemistry 26:5351–5358PubMedCrossRefGoogle Scholar
  43. 43.
    Varghese JN, Colman PM (1991) Three-dimensional structure of the neuraminidase of influenza virus A/Tokyo/3/67 at 2.2 A resolution. J Mol Biol 221:473–486PubMedCrossRefGoogle Scholar
  44. 44.
    Varghese JN, McKimm-Breschkin JL, Caldwell JB, Kortt AA, Colman PM (1992) The structure of the complex between influenza virus neuraminidase and sialic acid, the viral receptor. Proteins: Struct Funct Genet 14:327–332CrossRefGoogle Scholar
  45. 45.
    Colman PM, Varghese JN, Laver WG (1983) Structure of the catalytic and antigenic sites in influenza virus neuraminidase. Nature 303:41–44PubMedCrossRefGoogle Scholar
  46. 46.
    Koshland DE Jr (1953) Stereochemistry and the mechanism of enzymic reactions. Biol Rev Camb Philos Soc 28:416–436CrossRefGoogle Scholar
  47. 47.
    Vocadlo DJ, Davies GJ (2008) Mechanistic insights into glycosidase chemistry. Curr Opin Chem Biol 12:539–555PubMedCrossRefGoogle Scholar
  48. 48.
    Davies GJ, Ducros VMA, Varrot A, Zechel DL (2003) Mapping the conformational itinerary of β-glycosidases by X-ray crystallography. Biochem Soc Trans 31:523–527PubMedCrossRefGoogle Scholar
  49. 49.
    Davies GJ, Gloster TM, Henrissat B (2005) Recent structural insights into the expanding world of carbohydrate-active enzymes. Curr Opin Struct Biol 15:637–645PubMedCrossRefGoogle Scholar
  50. 50.
    Guo X, Laver WG, Vimr E, Sinnott ML (1994) Catalysis by two sialidases with the same protein fold but different stereochemical courses: a mechanistic comparison of the enzymes from influenza A virus and Salmonella typhimurium. J Am Chem Soc 116:5572–5578CrossRefGoogle Scholar
  51. 51.
    Narine AA, Watson JN, Bennet AJ (2006) Mechanistic requirements for efficient enzyme-catalyzed hydrolysis of thiosialosides. Biochemistry 45:9319–9326PubMedCrossRefGoogle Scholar
  52. 52.
    Watson JN, Dookhun V, Borgford TJ, Bennet AJ (2003) Mutagenesis of the conserved active-site tyrosine changes a retaining sialidase into an inverting sialidase. Biochemistry 42:12682–12690PubMedCrossRefGoogle Scholar
  53. 53.
    Chong AKJ, Pegg MS, Taylor NR, von Itzstein M (1992) Evidence for a sialosyl cation transition-state complex in the reactivity of sialidase from influenza virus. Eur J Biochem 207:335–343PubMedCrossRefGoogle Scholar
  54. 54.
    Barnes JA, Williams IH (1996) Quantum mechanical/molecular mechanical approaches to transition state structure: mechanism of sialidase action. Biochem Soc Trans 24:263–268PubMedGoogle Scholar
  55. 55.
    Thomas A, Jourand D, Bret C, Amara P, Field MJ (1999) Is there a covalent intermediate in the viral neuraminidase reaction? A hybrid potential free-energy study. J Am Chem Soc 121:9693–9702CrossRefGoogle Scholar
  56. 56.
    Mader MM, Bartlett PA (1997) Binding energy and catalysis: the implications for transition-state analogs and catalytic antibodies. Chem Rev 97:1281–1301PubMedCrossRefGoogle Scholar
  57. 57.
    Withers SG, Rupitz K, Street IP (1988) 2-Deoxy-2-fluoro-D-glycosyl fluorides. A new class of specific mechanism-based glycosidase inhibitors. J Biol Chem 263:7929–7932PubMedGoogle Scholar
  58. 58.
    Watts AG, Damager I, Amaya ML, Buschiazzo A, Alzari P, Frasch AC, Withers SG (2003) Trypanosoma cruzi trans-sialidase operates through a covalent sialyl-enzyme intermediate: tyrosine is the catalytic nucleophile. J Am Chem Soc 125:7532–7533PubMedCrossRefGoogle Scholar
  59. 59.
    Colli W (1993) Trans-sialidase – a unique enzyme-activity discovered in the protozoan Trypanosoma-cruzi. FASEB J 7:1257–1264PubMedGoogle Scholar
  60. 60.
    Parodi AJ, Pollevick GD, Mautner M, Buschiazzo A, Sanchez DO, Frasch ACC (1992) Identification of the gene(s) coding for the trans-sialidase of Trypanosoma cruzi. EMBO J 11:1705–1710PubMedGoogle Scholar
  61. 61.
    Amaya MF, Watts AG, Damager T, Wehenkel A, Nguyen T, Buschiazzo A, Paris G, Frasch AC, Withers SG, Alzari PM (2004) Structural insights into the catalytic mechanism of Trypanosoma cruzi trans-sialidase. Structure 12:775–784PubMedCrossRefGoogle Scholar
  62. 62.
    Watts AG, Oppezzo P, Withers SG, Alzari PM, Buschiazzo A (2006) Structural and kinetic analysis of two covalent sialosyl-enzyme intermediates on Trypanosoma rangeli sialidase. J Biol Chem 281:4149–4155PubMedCrossRefGoogle Scholar
  63. 63.
    Newstead SL, Potter JA, Wilson JC, Xu GG, Chien CH, Watts AG, Withers SG, Taylor GL (2008) The structure of Clostridium perfringens NanI sialidase and its catalytic intermediates. J Biol Chem 283:9080–9088PubMedCrossRefGoogle Scholar
  64. 64.
    Newstead S, Watson JN, Knoll TL, Bennet AJ, Taylor G (2005) Structure and mechanism of action of an inverting mutant sialidase. Biochemistry 44:9117–9122PubMedCrossRefGoogle Scholar
  65. 65.
    Bennet AJ, Kitos TE (2002) Mechanisms of glycopyranosyl and 5-thioglycopyranosyl transfer reactions in solution. J Chem Soc Perkin Trans 2:1207–1222Google Scholar
  66. 66.
    Jencks WP (1980) When Is an intermediate not an intermediate? Enforced mechanisms of general acid-base catalyzed, carbocation, carbanion and ligand exchange reactions. Acc Chem Res 13:161–169CrossRefGoogle Scholar
  67. 67.
    Yang J, Schenkman S, Horenstein BA (2000) Primary 13C and beta-secondary 2H KIEs for trans-sialidase. A snapshot of nucleophilic participation during catalysis. Biochemistry 39:5902–5910PubMedCrossRefGoogle Scholar
  68. 68.
    Crennell SJ, Garman EF, Philippon C, Vasella A, Laver WG, Vimr ER, Taylor GL (1996) The structures of Salmonella typhimurium LT2 neuraminidase and its complexes with three inhibitors at high resolution. J Mol Biol 259:264–280PubMedCrossRefGoogle Scholar
  69. 69.
    Ghate AA, Air GM (1998) Site-directed mutagenesis of catalytic residues of influenza virus neuraminidase as an aid to drug design. Eur J Biochem 58:320–331CrossRefGoogle Scholar
  70. 70.
    Kleineidam RG, Kruse S, Roggentin P, Schauer R (2001) Elucidation of the role of functional amino acid residues of the small sialidase from clostridium perfringens by site-directed mutagenesis. Biol Chem 382:313–319PubMedCrossRefGoogle Scholar
  71. 71.
    Wang Y, Yamaguchi K, Shimada Y, Zhao XJ, Miyagi T (2001) Site-directed mutagenesis of human membrane-associated ganglioside sialidase – Identification of amino-acid residues contributing to substrate specificity. Eur J Biochem 268:2201–2208PubMedCrossRefGoogle Scholar
  72. 72.
    Watson JN, Newstead S, Narine A, Taylor G, Bennet AJ (2005) Two nucleophilic mutants of the Micromonospora viridifaciens sialidase operate with retention of configuration via two different mechanisms. ChemBioChem 6:1999–2004PubMedCrossRefGoogle Scholar
  73. 73.
    Chien CH, Shann YJ, Sheu SY (1996) Site-directed mutations of the catalytic and conserved amino acids of the neuraminidase gene, nanH, of Clostridium perfringens ATCC 10543. Enzyme Microb Technol 19:267–276PubMedCrossRefGoogle Scholar
  74. 74.
    Wang QP, Graham RW, Trimbur D, Warren RAJ, Withers SG (1994) Changing enzymatic-reaction mechanisms by mutagenesis - conversion of a retaining glucosidase to an inverting enzyme. J Am Chem Soc 116:11594–11595CrossRefGoogle Scholar
  75. 75.
    Watson JN, Newstead S, Dookhun V, Taylor G, Bennet AJ (2004) Contribution of the active site aspartic acid to catalysis in the bacterial neuraminidase from Micromonospora viridifaciens. FEBS Lett 577:265–269PubMedCrossRefGoogle Scholar
  76. 76.
    Guo X, Sinnott ML (1993) A kinetic-isotope-effect study of catalysis by Vibrio cholerae neuraminidase. Biochem J 294:653–656PubMedGoogle Scholar

Copyright information

© Springer Basel AG 2012

Authors and Affiliations

  1. 1.Department of ChemistrySimon Fraser UniversityBurnabyCanada

Personalised recommendations