Identification of ß‐Glucocerebrosidase Activators for Glucosylceramide hydrolysis
Monika‐Sarah E. D. Schulze, Diana Scholz, Eric Jnoff, Adrian Hall, Jonathan Melin, Zara A. Sands, Elizabeth Rodríguez Acevedo, Véronique André
Abstract
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.
Topics & Concepts
GlucocerebrosidaseAllosteric regulationChemotypeDimerChemistryMonomerEnzymeStereochemistryBiophysicsBiochemistryBiologyPolymerOrganic chemistryChromatographyEssential oilLysosomal Storage Disorders ResearchCarbohydrate Chemistry and SynthesisBiomedical Research and Pathophysiology