3QZ2: The Structure Of Cysteine-free Human Insulin Degrading Enzyme

Citation:
Abstract
Insulin degrading enzyme (IDE) is a highly conserved zinc metalloprotease that is involved in the clearance of various physiologically peptides like amyloid-beta and insulin. This enzyme has been involved in the physiopathology of diabetes and Alzheimer's disease. We describe here a series of small molecules discovered by screening. Co-crystallization of the compounds with IDE revealed a binding both at the permanent exosite and at the discontinuous, conformational catalytic site. Preliminary structure-activity relationships are described. Selective inhibition of amyloid-beta degradation over insulin hydrolysis was possible. Neuroblastoma cells treated with the optimized compound display a dose-dependent increase in amyloid-beta levels.
PDB ID: 3QZ2Download
MMDB ID: 96679
PDB Deposition Date: 2011/3/4
Updated in MMDB: 2014/05
Experimental Method:
x-ray diffraction
Resolution: 3.2  Å
Source Organism:
Similar Structures:
Biological Unit for 3QZ2: dimeric; determined by author
Molecular Components in 3QZ2
Label Count Molecule
Proteins (2 molecules)
2
Insulin-degrading Enzyme(Gene symbol: IDE)
Molecule annotation
Chemicals (2 molecules)
1
2
* Click molecule labels to explore molecular sequence information.

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