Summary for 9FAL
| Entry DOI | 10.2210/pdb9fal/pdb |
| Descriptor | Lysosomal acid glucosylceramidase, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, 2-acetamido-2-deoxy-beta-D-glucopyranose, ... (9 entities in total) |
| Functional Keywords | glycosidase, cholesterol metabolism, steroid metabolism, glycosyl transferase, lipid binding protein |
| Biological source | Homo sapiens (human) |
| Total number of polymer chains | 1 |
| Total formula weight | 62898.28 |
| Authors | Tisi, D.,Cleasby, A. (deposition date: 2024-05-10, release date: 2024-07-03, Last modification date: 2024-10-16) |
| Primary citation | Palmer, N.,Agnew, C.,Benn, C.,Buffham, W.J.,Castro, J.N.,Chessari, G.,Clark, M.,Cons, B.D.,Coyle, J.E.,Dawson, L.A.,Hamlett, C.C.F.,Hodson, C.,Holding, F.,Johnson, C.N.,Liebeschuetz, J.W.,Mahajan, P.,McCarthy, J.M.,Murray, C.W.,O'Reilly, M.,Peakman, T.,Price, A.,Rapti, M.,Reeks, J.,Schopf, P.,St-Denis, J.D.,Valenzano, C.,Wallis, N.G.,Walser, R.,Weir, H.,Wilsher, N.E.,Woodhead, A.,Bento, C.F.,Tisi, D. Fragment-Based Discovery of a Series of Allosteric-Binding Site Modulators of beta-Glucocerebrosidase. J.Med.Chem., 67:11168-11181, 2024 Cited by PubMed Abstract: β-Glucocerebrosidase (GBA/GCase) mutations leading to misfolded protein cause Gaucher's disease and are a major genetic risk factor for Parkinson's disease and dementia with Lewy bodies. The identification of small molecule pharmacological chaperones that can stabilize the misfolded protein and increase delivery of degradation-prone mutant GCase to the lysosome is a strategy under active investigation. Here, we describe the first use of fragment-based drug discovery (FBDD) to identify pharmacological chaperones of GCase. The fragment hits were identified by using X-ray crystallography and biophysical techniques. This work led to the discovery of a series of compounds that bind GCase with nM potency and positively modulate GCase activity in cells. PubMed: 38932616DOI: 10.1021/acs.jmedchem.4c00702 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.39 Å) |
Structure validation
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