3RME: Amcase In Complex With Compound 5

Acidic mammalian chitinase (AMCase) is a member of the glycosyl hydrolase 18 family (EC that has been implicated in the pathophysiology of allergic airway disease such as asthma. Small molecule inhibitors of AMCase were identified using a combination of high-throughput screening, fragment screening, and virtual screening techniques and characterized by enzyme inhibition and NMR and Biacore binding experiments. X-ray structures of the inhibitors in complex with AMCase revealed that the larger more potent HTS hits, e.g. 5-(4-(2-(4-bromophenoxy)ethyl)piperazine-1-yl)-1H-1,2,4-triazol-3-amine 1, spanned from the active site pocket to a hydrophobic pocket. Smaller fragments identified by FBS occupy both these pockets independently and suggest potential strategies for linking fragments. Compound 1 is a 200 nM AMCase inhibitor which reduced AMCase enzymatic activity in the bronchoalveolar lavage fluid in allergen-challenged mice after oral dosing.
PDB ID: 3RMEDownload
MMDB ID: 92906
PDB Deposition Date: 2011/4/20
Updated in MMDB: 2011/08
Experimental Method:
x-ray diffraction
Resolution: 1.8  Å
Source Organism:
Similar Structures:
Biological Unit for 3RME: monomeric; determined by author and by software (PISA)
Molecular Components in 3RME
Label Count Molecule
Protein (1 molecule)
Acidic Mammalian Chitinase(Gene symbol: CHIA)
Molecule annotation
Chemicals (2 molecules)
* Click molecule labels to explore molecular sequence information.

Citing MMDB