Multivalency and the mode of action of bacterial sialidases

Smita Thobhani, Brian Ember, Aloysius Siriwardena, Geert Jan Boons*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)7154-7155
Number of pages2
JournalJournal of the American Chemical Society
Volume125
Issue number24
DOIs
Publication statusPublished - 18 Jun 2003
Externally publishedYes

Fingerprint

Dive into the research topics of 'Multivalency and the mode of action of bacterial sialidases'. Together they form a unique fingerprint.

Cite this