Known alternatively as insulysin or insulin protease, the insulin-degrading enzyme (IDE) is a large zinc-binding protease of the M16 metalloprotease family known to cleave multiple short polypeptides that vary considerably in sequence. Other members of this family include the mitochondrial processing peptidase and presequence protease. IDE was first identified by its ability to degrade the B chain of the hormone insulin. This activity was observed over sixty years ago, though the enzyme specifically responsible for B chain cleavage was identified more recently. This discovery revealed considerable amino acid sequence similarity between IDE and the previously characterized bacterial protease pitrilysin, suggesting a common proteolytic mechanism. Considerable interest in IDE has been stimulated due to the discovery that IDE can degrade amyloid beta (Aβ), a peptide implicated in the pathogenesis of Alzheimer's disease. Numerous in vitro and in vivo studies have shown correlations between IDE, Aβ degradation, and Alzheimer’s disease. Mice engineered to lack both alleles of the IDE gene exhibit a 50% decrease in Aβ degradation, resulting in cerebral accumulation of Aβ. Studies of genetically inherited forms of Alzheimer’s show reduction in both IDE expression and catalytic activity among affected individuals. Despite the evident role of IDE in disease, relatively little is known about its physiological functions. These may be diverse, as IDE has been localized to several locations, including the cytosol, peroxisomes, endosomes, proteasome complexes, and the surface of cerebrovascular endothelial cells. Here you can see a high-resolution cryoEM structure of human IDE in its dimeric form (PDB code: 7RZI)
#molecularart ... #immolecular ... #cryoem ... #insulin ... #degrading ... #protease ... #alzheimer
Structure rendered with @proteinimaging and depicted with @corelphotopaint
#molecularart ... #immolecular ... #cryoem ... #insulin ... #degrading ... #protease ... #alzheimer
Structure rendered with @proteinimaging and depicted with @corelphotopaint
