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Article Dans Une Revue Angewandte Chemie International Edition Année : 2018

Structural Basis of Outstanding Multivalent Effects in Jack Bean α-Mannosidase Inhibition

Résumé

Multivalent design of glycosidase inhibitors is a promising strategy for the treatment of diseases involving enzymatic hydrolysis of glycosidic bonds in carbohydrates. An essential prerequisite for successful applications is the atomic-level understanding of how outstanding binding enhancement occurs with multivalent inhibitors. Herein we report the first high-resolution crystal structures of the Jack bean α-mannosidase (JBα-man) in apo and inhibited states. The three-dimensional structure of JBα-man in complex with the multimeric cyclopeptoid-based inhibitor displaying the largest binding enhancements reported so far provides decisive insight into the molecular mechanisms underlying multivalent effects in glycosidase inhibition.

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Domaines

Chimie organique

Dates et versions

hal-02177420 , version 1 (08-07-2019)

Identifiants

Citer

E Howard, A Cousido-Siah, Mathieu Lepage, Jérémy Schneider, Anne Bodlenner, et al.. Structural Basis of Outstanding Multivalent Effects in Jack Bean α-Mannosidase Inhibition. Angewandte Chemie International Edition, 2018, 57 (27), pp.8002-8006. ⟨10.1002/anie.201801202⟩. ⟨hal-02177420⟩
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