5OST
Beta-glucosidase from Thermoanaerobacterium xylolyticum GH116 in complex with Gluco-1H-imidazole
Summary for 5OST
| Entry DOI | 10.2210/pdb5ost/pdb |
| Descriptor | Glucosylceramidase, CALCIUM ION, 1,2-ETHANEDIOL, ... (6 entities in total) |
| Functional Keywords | hydrolase |
| Biological source | Thermoanaerobacterium xylanolyticum (strain ATCC 49914 / DSM 7097 / LX-11) |
| Total number of polymer chains | 1 |
| Total formula weight | 92708.26 |
| Authors | Davies, G.J.,Offen, W.A. (deposition date: 2017-08-18, release date: 2018-04-11, Last modification date: 2024-01-17) |
| Primary citation | Schroder, S.P.,Wu, L.,Artola, M.,Hansen, T.,Offen, W.A.,Ferraz, M.J.,Li, K.Y.,Aerts, J.M.F.G.,van der Marel, G.A.,Codee, J.D.C.,Davies, G.J.,Overkleeft, H.S. Gluco-1 H-imidazole: A New Class of Azole-Type beta-Glucosidase Inhibitor. J. Am. Chem. Soc., 140:5045-5048, 2018 Cited by PubMed Abstract: Gluco-azoles competitively inhibit glucosidases by transition-state mimicry and their ability to interact with catalytic acid residues in glucosidase active sites. We noted that no azole-type inhibitors described, to date, possess a protic nitrogen characteristic for 1 H-imidazoles. Here, we present gluco-1 H-imidazole, a gluco-azole bearing a 1 H-imidazole fused to a glucopyranose-configured cyclitol core, and three close analogues as new glucosidase inhibitors. All compounds inhibit human retaining β-glucosidase, GBA1, with the most potent ones inhibiting this enzyme (deficient in Gaucher disease) on a par with glucoimidazole. None inhibit glucosylceramide synthase, cytosolic β-glucosidase GBA2 or α-glucosidase GAA. Structural, physical and computational studies provide first insights into the binding mode of this conceptually new class of retaining β-glucosidase inhibitors. PubMed: 29601200DOI: 10.1021/jacs.8b02399 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.1 Å) |
Structure validation
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