2YBT
Crystal structure of human acidic chitinase in complex with bisdionin C
Summary for 2YBT
| Entry DOI | 10.2210/pdb2ybt/pdb |
| Related | 2YBU |
| Descriptor | ACIDIC MAMMALIAN CHITINASE, GLYCEROL, 1,1'-PROPANE-1,3-DIYLBIS(3,7-DIMETHYL-3,7-DIHYDRO-1H-PURINE-2,6-DIONE), ... (4 entities in total) |
| Functional Keywords | hydrolase |
| Biological source | HOMO SAPIENS (HUMAN) |
| Cellular location | Isoform 1: Secreted. Isoform 2: Cytoplasm. Isoform 3: Cytoplasm: Q9BZP6 |
| Total number of polymer chains | 6 |
| Total formula weight | 261116.99 |
| Authors | Sutherland, T.E.,Andersen, O.A.,Betou, M.,Eggleston, I.M.,Maizels, R.M.,van Aalten, D.,Allen, J.E. (deposition date: 2011-03-10, release date: 2011-06-08, Last modification date: 2024-10-16) |
| Primary citation | Sutherland, T.E.,Andersen, O.A.,Betou, M.,Eggleston, I.M.,Maizels, R.M.,van Aalten, D.,Allen, J.E. Analyzing airway inflammation with chemical biology: dissection of acidic mammalian chitinase function with a selective drug-like inhibitor. Chem. Biol., 18:569-579, 2011 Cited by PubMed Abstract: Acidic mammalian chitinase (AMCase) is produced in the lung during allergic inflammation and asthma, and inhibition of enzymatic activity has been considered as a therapeutic strategy. However, most chitinase inhibitors are nonselective, additionally inhibiting chitotriosidase activity. Here, we describe bisdionin F, a competitive AMCase inhibitor with 20-fold selectivity for AMCase over chitotriosidase, designed by utilizing the AMCase crystal structure and dicaffeine scaffold. In a murine model of allergic inflammation, bisdionin F-treatment attenuated chitinase activity and alleviated the primary features of allergic inflammation including eosinophilia. However, selective AMCase inhibition by bisdionin F also caused dramatic and unexpected neutrophilia in the lungs. This class of inhibitor will be a powerful tool to dissect the functions of mammalian chitinases in disease and represents a synthetically accessible scaffold to optimize inhibitory properties in terms of airway inflammation. PubMed: 21609838DOI: 10.1016/j.chembiol.2011.02.017 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.22 Å) |
Structure validation
Download full validation report
