2YBT: Crystal structure of human acidic chitinase in complex with bisdionin C

Citation:
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.
PDB ID: 2YBTDownload
MMDB ID: 91147
PDB Deposition Date: 2011/3/10
Updated in MMDB: 2011/06
Experimental Method:
x-ray diffraction
Resolution: 2.22  Å
Source Organism:
Similar Structures:
Biological Unit for 2YBT: monomeric; determined by author and by software (PISA)
Molecular Components in 2YBT
Label Count Molecule
Protein (1 molecule)
1
Acidic Mammalian Chitinase(Gene symbol: CHIA)
Molecule annotation
Chemicals (4 molecules)
1
1
2
3
* Click molecule labels to explore molecular sequence information.

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