The interaction of substrate-related ketals with bacterial and viral neuraminidases |
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Authors: | Michael Flashner Jack Kessler Stuart W. Tanenbaum |
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Affiliation: | Department of Chemistry, State University of New York, College of Environmental Science and Forestry, Syracuse, New York 13210 USA |
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Abstract: | Arthrobacter sialophilus neuraminidase catalyzes the hydration of 5-acetamido-2,6-anhydro-3, 5-dideoxy-d-glycero-d-galacto-non-2-enonic acid (2,3-dehydro-AcNeu) with Km and kcat values of 8.9 × 10?4m and 6.40 × 10?4 s?1, respectively. The methyl ester of 2,3-dehydro-AcNeu as well as 2,3-dehydro-4-epi-AcNeu are also hydrated by the enzyme. The product resulting from the enzymatic hydration of 2,3-dehydro-AcNeu is N-acetylneuraminic acid. A series of derivatives of 2,3-dehydro-AcNeu (KI 1.60 × 10?6m) including 2,3-dehydro-4-epi-AcNeu (2.10 × 10?4m) and 2,3-dehydro-4-keto-AcNeu (KI = 6.10 × 10?5 m) were each competitive inhibitors of the enzyme. The methyl esters of these ketal derivatives were also competitive enzyme inhibitors. Dissociation constants for these ketals were determined independently by fluorescence enzyme titrations which gave values similar to those found kinetically. These six relatives of 2,3-dehydro-AcNeu were also competitive inhibitors for the influenza viral neuraminidases. For the viral neuraminidases, the dissociation constant for 2,3-dehydro-AcNeu and its methyl ester were 2.40 × 10?6 and 1.17 × 10?3m, respectively. The interpretation placed upon the KI values determined for these ketals against the Arthrobacter versus influenza neuraminidases is that the bacterial enzyme has a more flexible glycone binding site. |
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Keywords: | Author to whom all correspondence should be addressed. |
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