IDE Human
Description
Product Specs
Insulin-Degrading Enzyme (IDE) is a zinc metallopeptidase responsible for degrading intracellular insulin, thereby ending its activity. It also contributes to intercellular peptide signaling by breaking down various peptides such as amylin, bradykinin, and kallidin. IDE's strong affinity for insulin leads to insulin-mediated inhibition of the degradation of other peptides like beta-amyloid. Impaired IDE function is associated with Alzheimer's disease and type 2 diabetes mellitus, although mutations in the IDE gene haven't been proven as a direct cause of these diseases. IDE is primarily found in the cytoplasm, but in certain cell types, it can also be located in the extracellular space, cell membrane, peroxisome, and mitochondrion. Moreover, IDE degrades amyloid generated by APP and IAPP and participates in the degradation and clearance of naturally secreted amyloid beta-protein by neurons and microglia.
IDE, filtered through a 0.4µm filter, is supplied in a solution of 20mM Tris buffer, 50mM NaCl, at pH 8.0, with 10% (w/v) glycerol.
Product Science Overview
IDE was first identified over sixty years ago due to its ability to degrade the B chain of insulin . The enzyme responsible for this activity was later identified and characterized. The discovery of IDE’s role in insulin degradation has significant implications for understanding insulin regulation and its termination of activity in insulin-responsive tissues .
IDE is composed of two homologous ~55 kDa N- and C-terminal halves, which form a large opening that allows selective substrate capture based on size and charge complementarity . This structural feature is crucial for IDE’s ability to degrade amyloidogenic peptides, including insulin and amyloid β-protein (Aβ), which are associated with type 2 diabetes mellitus and Alzheimer’s disease .
IDE degrades insulin by stochastically cutting either chain without breaking disulfide bonds . This processive degradation is facilitated by the enzyme’s catalytic cleft, which is stabilized by amyloidogenic peptides through substrate-assisted catalysis . The enzyme’s ability to degrade various peptides, such as amylin, bradykinin, and kallidin, highlights its role in intercellular peptide signaling .
The human recombinant form of IDE has been successfully expressed in Chinese hamster ovary cells using a plasmid containing the IDE cDNA under the transcriptional control of the SRα promoter . The recombinant protein synthesized by these cells is indistinguishable from the isolated human enzyme in both size and immunoreactivity, and it degrades insulin with a specific activity similar to that of the purified proteinase .
IDE’s role in degrading insulin and amyloidogenic peptides makes it a potential therapeutic target for diseases such as type 2 diabetes and Alzheimer’s disease . Understanding the molecular basis of IDE’s function and its interaction with substrates can aid in the development of IDE-based therapies .
