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Insulin-degrading enzyme (4PES)11 is composed of four domains. The N-terminal half of IDE (IDEN, domains 1 and 2) is linked to the C-terminal half (IDEC, domains 3 and 4) by a flexible linker (purple). Domain 1 contains Zn2+ coordinated to H108 and H112 and the catalytically active residue (E111, mutated to a glutamine in 4PES). Domain 2 contains a highly conserved exosite (red) that is hypothesized to be important for the binding of substrates prior to degradation.
