Sialidases: Structures, biological significance and therapeutic potential

Current Opinion in Structural Biology

Volumn 6, Issue 6, 1996, Pages 830-837

  Taylor, Garry ^a  

^a UNIVERSITY OF BATH   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

BACTERIAL ENZYME; ENZYME INHIBITOR; SIALIDASE; VIRUS ENZYME; ZANAMIVIR;

BACTERIOPHAGE; DRUG DESIGN; DRUG PROTEIN BINDING; ENZYME CONFORMATION; ENZYME INHIBITION; ENZYME INHIBITOR INTERACTION; ENZYME STRUCTURE; HUMAN; INFLUENZA; INFLUENZA VIRUS; NONHUMAN; PRIORITY JOURNAL; REVIEW; TRYPANOSOMA; VIRUS MUTANT;

BACTERIA (MICROORGANISMS); HUMAN INFLUENZA VIRUS; INFLUENZA VIRUS; TRYPANOSOMA;

EID: 0030444832     PISSN: 0959440X     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0959-440X(96)80014-5     Document Type: Article

References (54)

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23. Chuenkova M, Pareira MEA: Trypanosoma cruzi trans-sialidase enhancement of virulence in a mUri ne model of Chagas disease. J Ejp Medicine 1995, 181:1693-1 703. Another in a series of papers that are beginning to shed light on the importance and biological functions of the TS- Mice are sensitized with purified TCTS before being inoculated with trypanosomes. Such sensitization greatly enhanced parasitemia and mortality. This virulence-enhancing effect of TCTS appears to depend on inflammatory cells, and is not produced by Newcastle disease HN or V, cholerae sialidase.
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35. Cremona ML, Sandier DO, Frasch ACC, Campetella O: A single tyrosine differentiates active and inactive Ttypanosoma cruzi trans-sialdiases. Gene 1995, 160:123-128. Two genes of the TS family - one enzymaticalty active, the olher not - are sequenced. Only one of the 20 amino acid differences between the gene products - Tyr342, which is a histidine in the inactive protein - is found to be essential for enzyme activity. Using the structure of Ihe S. typhrmurium sialidase, 1 4 of 16 active site residues are found to be conserved in the TS seqeunce, including Tyr342. The role of this tryosine in Ihe bacterial enzyme is thought to be in stabilizing the oxocarbonium ion intermediate. However, the mechanism of TS is likely to be quite different from that of the sialidase,
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37. Woods JM, Bethetl RC, Coales JAV, Healy N, Hiscox SA, Pearson BA, Ryan DM, Ticehurst J, Walcott SM, Penn CR: 4-guanidino 2,4-dideoxy 2,3-dehydro-yV-acetyl neurammic acid is a highly effective inhibitor both of the sialidase (neuraminidase) and of growth of a wide range of influenza A and B viruses in vitro. Antimicrob Agents Cheirtother 1993, 37:1473-1479.
38. Hayden FG, Treanor JJ, Betts R F, Lobo M, Esinhart JD, Hussey EK: Safety and efficacy of the neuraminidase inhibitor GG1E7 in experimental human influenza. J Am Med Assoc 1996, 275:235-299. GG167 is administered intranasally to human volunteers, either as a prophylactic, starting 4 hours before innoculation, or as an early treatment, 1 to 2 days afterwards. The drug is found to be 85% effective in prophylaxis, that is in prevenling laboratory evidence of infection, and is also found to be effective as an early treatment Twice daily dosing is shown to be as effective as dosing si timss daily.
39. Gubareva LV, Penn CR, Webster RG: Inhibition of replication of avian influenza viruses by the neuraminidase inhibitor 4guanidino-2,4-dideoxy-2,3-dehydro-W-acetylneuraminic acid. Virology 1995, 212:323-330. GG167 inhibits influenza virus neuraminidases from all nine subtypes of avian influenza virus in vitro. However, when given inlranasally 1o chickens infected with lethal viruses, high doses protected 85% of birds with an H7N7 strain, but not those with viruses of Ihe NI, N2 or N3 subtypes. These differential effects suggest that the systems exhibit differences in penetration and attachment.
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49. Jedrzejas MJ, Singh S, Brouillelte WJ, Air GM, Luo M: A strategy for theoretical binding constant, Kj, calculations for neuraminidase aromatic inhibitors designed on the basis of the active-site structure of influenza virus neuraminidase. Proteins 1 995, 23:264-277. Ar interesting use of DelPhi to calculate binding affinities for newly designed inhibitors. Applied to the benzoic-acid family of analogues, the calculated K,s show remarkable agreements with their biological activities.
50. Blick TJ, Tiong T, Sahasrabudhe A, Varghese JN, Colman PM, Hart GJ, Bethell RC, McKimm-Breschkin JL: Generation and characterization of a influenza virus neuraminidase variant with decreased sensitivity to the neuraminidase-specific inhibitor 4-guanidino-Neu5Ac2en. Virology1995, 214:476-484 In vitro experiments show that virus grown in MDCK cells in the presence of GG167 mutate Glu119 to a glycine. These viruses are 1000-fold less sensitive to GG167 in a plaque assay. In an enzyme inhibition assay, 250-fold more drug is needed to achieve the same inhibition as the parent virus. In contrast, 4-amino-Neu5Ac2en shows similar binding and inhibition to both parent and mutant viruses. Crystallographic analyses suggest that the reduced affinity of GG167 arises from both the loss of Glu119 and from alterations in the solvent structure.
51. Staschke KA, Colacino JM, Baxter AJ, Air GM, Bansal A, Hornback WJ, Munroe JE, Laver WO: Molecular basis for the resistance of influenza viruses to 4-guanidino-Neu5Ac2en. Virology 1 995, 214:642-646 A similar study to the previous paper, showing the generation ot a resistant virus in vitro with the same Glu119 to glycine mutation. The enzyme activity of the mutant is reduced by 95%. This suggests an important role for Glul 19 in the catalytic mechanism, as the structure of the mutant (described in [50"]) shows no apparent differences in the active site Much still needs to be done in understanding the mechanism1
52. Angus DI, Von Itzstem M: Towards the synthesis of sialic acid-based Salmonella typhimurium sialidase inhibitors. Carbohydrate Res 1995, 274:279-283
53. Crennell SJ, Garnian EF, Laver WG, Vimr ER. Phillipon G, Vassella A, Taylor GL : The structure of Salmonella typhimurium sialidase and its complexes with three inhibitors at high resolution. J Mol Biol 1996, 259:264-280.
54. Crennell SJ, Garnian EF, Laver WG, Vimr ER. Phillipon G, Vassella A, Taylor GL : The structure of Salmonella typhimurium sialidase and its complexes with three inhibitors at high resolution. J Mol Biol 1996, 259:264-280.