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

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 occur...

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Autores principales: Howard, Eduardo Ignacio, Cousido Siah, Alexandra, Lepage, Mathieu L., Schneider, Jérémy P., Bodlenner, Anne, Mitschler, André, Meli, Alessandra, Izzo, Irene, Álvarez, Hugo Ariel, Podjarny, Alberto, Compain, Philippe
Formato: Articulo Preprint
Lenguaje:Inglés
Publicado: 2018
Materias:
Química
Cyclic peptoids
Hydrolases
Iminosugars
Multivalency
X-ray diffraction
Acceso en línea:http://sedici.unlp.edu.ar/handle/10915/96218
https://ri.conicet.gov.ar/11336/87935
http://doi.wiley.com/10.1002/anie.201801202
Aporte de:
SEDICI (UNLP) de Universidad Nacional de La Plata
id I19-R120-10915-96218
record_format dspace
institution Universidad Nacional de La Plata
institution_str I-19
repository_str R-120
collection SEDICI (UNLP)
language Inglés
topic Química
Cyclic peptoids
Hydrolases
Iminosugars
Multivalency
X-ray diffraction
spellingShingle Química
Cyclic peptoids
Hydrolases
Iminosugars
Multivalency
X-ray diffraction
Howard, Eduardo Ignacio
Cousido Siah, Alexandra
Lepage, Mathieu L.
Schneider, Jérémy P.
Bodlenner, Anne
Mitschler, André
Meli, Alessandra
Izzo, Irene
Álvarez, Hugo Ariel
Podjarny, Alberto
Compain, Philippe
Structural Basis of Outstanding Multivalent Effects in Jack Bean α-Mannosidase Inhibition
topic_facet Química
Cyclic peptoids
Hydrolases
Iminosugars
Multivalency
X-ray diffraction
description 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.
format Articulo
Preprint
author Howard, Eduardo Ignacio
Cousido Siah, Alexandra
Lepage, Mathieu L.
Schneider, Jérémy P.
Bodlenner, Anne
Mitschler, André
Meli, Alessandra
Izzo, Irene
Álvarez, Hugo Ariel
Podjarny, Alberto
Compain, Philippe
author_facet Howard, Eduardo Ignacio
Cousido Siah, Alexandra
Lepage, Mathieu L.
Schneider, Jérémy P.
Bodlenner, Anne
Mitschler, André
Meli, Alessandra
Izzo, Irene
Álvarez, Hugo Ariel
Podjarny, Alberto
Compain, Philippe
author_sort Howard, Eduardo Ignacio
title Structural Basis of Outstanding Multivalent Effects in Jack Bean α-Mannosidase Inhibition
title_short Structural Basis of Outstanding Multivalent Effects in Jack Bean α-Mannosidase Inhibition
title_full Structural Basis of Outstanding Multivalent Effects in Jack Bean α-Mannosidase Inhibition
title_fullStr Structural Basis of Outstanding Multivalent Effects in Jack Bean α-Mannosidase Inhibition
title_full_unstemmed Structural Basis of Outstanding Multivalent Effects in Jack Bean α-Mannosidase Inhibition
title_sort structural basis of outstanding multivalent effects in jack bean α-mannosidase inhibition
publishDate 2018
url http://sedici.unlp.edu.ar/handle/10915/96218
https://ri.conicet.gov.ar/11336/87935
http://doi.wiley.com/10.1002/anie.201801202
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