Identification of ß-Glucocerebrosidase Activators for Glucosylceramide hydrolysis

Identification of ß-Glucocerebrosidase Activators for Glucosylceramide hydrolysis

Several novel chemical series were identified that modulate glucocerebrosidase (GCase). Compounds from these series are active on glucosylceramide, unlike other known GCase modulators. We obtained GCase crystal structures with two compounds that have distinct chemotypes. Positive allosteric modulato...

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Veröffentlicht in:ChemMedChem 2024-04, Vol.19 (7), p.e202300548-e202300548
Hauptverfasser: Schulze, Monika-Sarah E D, Scholz, Diana, Jnoff, Eric, Hall, Adrian, Melin, Jonathan, Sands, Zara A, Rodriguez, Elizabeth, Andre, Veronique M
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Allosteric properties
Glucosylceramidase
Modulators
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container_end_page e202300548
container_issue 7
container_start_page e202300548
container_title ChemMedChem
container_volume 19
creator Schulze, Monika-Sarah E D
Scholz, Diana
Jnoff, Eric
Hall, Adrian
Melin, Jonathan
Sands, Zara A
Rodriguez, Elizabeth
Andre, Veronique M
description Several novel chemical series were identified that modulate glucocerebrosidase (GCase). Compounds from these series are active on glucosylceramide, unlike other known GCase modulators. We obtained GCase crystal structures with two compounds that have distinct chemotypes. Positive allosteric modulators bind to a site on GCase and induce conformational changes, but also induce an equilibrium state between monomer and dimer.
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subjects Allosteric properties
Glucosylceramidase
Modulators
title Identification of ß-Glucocerebrosidase Activators for Glucosylceramide hydrolysis
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