8P3E

Crystal structure of glucocerebrosidase in complex with allosteric activator

Summary for 8P3E

• Entry DOI: 10.2210/pdb8p3e/pdb
• Descriptor: Glucosylceramidase, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, 2-acetamido-2-deoxy-beta-D-glucopyranose, ... (5 entities in total)
• Functional Keywords: activator, lysosome, glycolipid metabolism, hydrolase
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 2
• Total formula weight: 112578.01

Authors

Schulze, M.-S. (deposition date: 2023-05-17, release date: 2024-03-06, Last modification date: 2024-11-06)

Primary citation

Schulze, M.E.D.,Scholz, D.,Jnoff, E.,Hall, A.,Melin, J.,Sands, Z.A.,Rodriguez, E.,Andre, V.M.
Identification of ss-Glucocerebrosidase Activators for Glucosylceramide hydrolysis.
Chemmedchem, 19:e202300548-e202300548, 2024

PubMed 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.

PubMed: 38381042
DOI: 10.1002/cmdc.202300548

Experimental method

X-RAY DIFFRACTION (1.75 Å)