Download MendeleyStructural Basis of Outstanding Multivalent Effects in Jack Bean alpha-Mannosidase Inhibition.
Howard, E., Cousido-Siah, A., Lepage, M.L., Schneider, J.P., Bodlenner, A., Mitschler, A., Meli, A., Izzo, I., Alvarez, H.A., Podjarny, A., Compain, P.(2018) Angew Chem Int Ed Engl 57: 8002-8006
- PubMed: 29722924
- DOI: https://doi.org/10.1002/anie.201801202
- Primary Citation of Related Structures:
6B9O, 6B9P - PubMed 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.
Organizational Affiliation:
Department of Integrative Biology, Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS, INSERM, UdS, 1 rue Laurent Fries, 67404, Illkirch CEDEX, France.
