6MOZ
Structure of acid-beta-glucosidase in complex with an aromatic pyrrolidine iminosugar inhibitor
Summary for 6MOZ
| Entry DOI | 10.2210/pdb6moz/pdb |
| Descriptor | Glucosylceramidase, 2-acetamido-2-deoxy-beta-D-glucopyranose, SODIUM ION, ... (7 entities in total) |
| Functional Keywords | tim-barrel, glycosidase, cerezyme, hydrolysis, hydrolase, inhibitor complex, pharmacological chaperone |
| Biological source | Homo sapiens (Human) |
| Total number of polymer chains | 2 |
| Total formula weight | 113449.53 |
| Authors | Patterson-Orazem, A.C.,Lieberman, R.L. (deposition date: 2018-10-05, release date: 2019-06-19, Last modification date: 2024-11-13) |
| Primary citation | Martinez-Bailen, M.,Carmona, A.T.,Patterson-Orazem, A.C.,Lieberman, R.L.,Ide, D.,Kubo, M.,Kato, A.,Robina, I.,Moreno-Vargas, A.J. Exploring substituent diversity on pyrrolidine-aryltriazole iminosugars: Structural basis of beta-glucocerebrosidase inhibition. Bioorg.Chem., 86:652-664, 2019 Cited by PubMed Abstract: The synthesis of a library of pyrrolidine-aryltriazole hybrids through CuAAC between two epimeric dihydroxylated azidomethylpyrrolidines and differently substituted phenylacetylenes is reported. The evaluation of the new compounds as inhibitors of lysosomal β-glucocerebrosidase showed the importance of the substitution pattern of the phenyl moiety in the inhibition. Crystallization and docking studies revealed key interactions of the pyrrolidine motif with aminoacid residues of the catalytic site while the aryltriazole moiety extended along a hydrophobic surface groove. Some of these compounds were able to increase the enzyme activity in Gaucher patient fibroblasts, acting as a new type of chemical chaperone for Gaucher disease. PubMed: 30825709DOI: 10.1016/j.bioorg.2019.02.025 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.1 Å) |
Structure validation
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