Multivalency and the Mode of Action of Bacterial Sialidases

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• 作者：Smita Thobhani ; Brian Ember ; Aloysius Siriwardena ; and Geert-Jan Boons
• 刊名：Journal of the American Chemical Society
• 出版年：2003
• 出版时间：June 18, 2003
• 年：2003
• 卷：125
• 期：24
• 页码：7154 - 7155
• 全文大小：43K
• 年卷期：v.125,no.24(June 18, 2003)
• ISSN：1520-5126

文摘

Although complex modular proteins are encountered frequently in a variety of biological systems, their occurrence in biocatalysis has not been widely appreciated. Here, we describe that bacterial sialidases, which have both a catalytic and carbohydrate-binding domain, can hydrolyze polyvalent substrates with much greater catalytic efficiency than their monovalent counterparts. The enhancement of catalytic efficiency was due to a much smaller Michaelis constant and rationalized by a model in which the catalytic and lectin domains interact simultaneously with the polyvalent substrate, leading to an enhancement of affinity. Inhibition studies have shown that galactosides released by the action of the sialidase can act as the ligand for the lectin domain. This knowledge has been exploited in the design of a potent polyvalent inhibitor of the sialidase of Vibrio cholerae, which displayed exquisite selectivities for sialidases that have a lectin domain.