2IUZ: Crystal Structure Of Aspergillus Fumigatus Chitinase B1 In Complex With C2-Dicaffeine

Family 18 chitinases play key roles in the life cycles of a variety of organisms ranging from bacteria to man. Very recently it has been shown that one of the mammalian chitinases is highly overexpressed in the asthmatic lung and contributes to the pathogenic process through recruitment of inflammatory cells. Although several potent natural product chitinase inhibitors have been identified, their chemotherapeutic potential or their use as cell biological tools is limited due to their size, complex chemistry, and limited availability. We describe a virtual screening-based approach to identification of a novel, purine-based, chitinase inhibitor. This inhibitor acts in the low micromolar (Ki=2.8+/-0.2 microM) range in a competitive mode. Dissection of the binding mode by x-ray crystallography reveals that the compound, which consists of two linked caffeine moieties, binds in the active site through extensive and not previously observed stacking interactions with conserved, solvent exposed tryptophans. Such exposed aromatics are also present in the structures of many other carbohydrate processing enzymes. The compound exhibits favorable chemical properties and is likely to be useful as a general scaffold for development of pan-family 18 chitinase inhibitors.
PDB ID: 2IUZDownload
MMDB ID: 40140
PDB Deposition Date: 2006/6/8
Updated in MMDB: 2012/11
Experimental Method:
x-ray diffraction
Resolution: 1.95  Å
Source Organism:
Similar Structures:
Biological Unit for 2IUZ: monomeric; determined by author and by software (PQS)
Molecular Components in 2IUZ
Label Count Molecule
Protein (1 molecule)
Molecule annotation
Chemicals (7 molecules)
* Click molecule labels to explore molecular sequence information.

Citing MMDB