Structural Basis of Outstanding Multivalent Effects in Jack Bean α-Mannosidase Inhibition.
Angew Chem Int Ed Engl
; 57(27): 8002-8006, 2018 07 02.
Article
en En
| MEDLINE
| ID: mdl-29722924
ABSTRACT
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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Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Alfa-Manosidasa
Idioma:
En
Año:
2018
Tipo del documento:
Article