Premium
Structural Basis of Outstanding Multivalent Effects in Jack Bean α‐Mannosidase Inhibition
Author(s) -
Howard Eduardo,
CousidoSiah Alexandra,
Lepage Mathieu L.,
Schneider Jérémy P.,
Bodlenner Anne,
Mitschler André,
Meli Alessandra,
Izzo Irene,
Alvarez H. Ariel,
Podjarny Alberto,
Compain Philippe
Publication year - 2018
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201801202
Subject(s) - glycoside hydrolase , mannosidase , glycosidic bond , chemistry , swainsonine , enzyme , biochemistry , stereochemistry
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.