8P41

Crystal structure of glucocerebrosidase in complex with allosteric activator

Summary for 8P41

Entry DOI	10.2210/pdb8p41/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, ... (6 entities in total)
Functional Keywords	activator, lysosome, glycolipid metabolism, hydrolase
Biological source	Homo sapiens (human)
Total number of polymer chains	2
Total formula weight	114406.55
Authors	Schulze, M.-S. (deposition date: 2023-05-18, 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 Cited by 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 PDB entries with the same primary citation
Experimental method	X-RAY DIFFRACTION (1.83 Å)

Structure validation