Elucidation of the metal-binding site in C-peptide, a hormone related to insulin

Schematic of the copper(II) binding site on proinsulin C-peptide (taken from Heffern and coworkers) with background figures depicting data collected from electron paramagnetic resonance (NMR), mass spectrometry (MS), nuclear magnetic resonance (NMR), and isothermal titration calorimetry (ITC).
Schematic of the copper(II) binding site on proinsulin C-peptide (taken from Heffern and coworkers) with background figures depicting data collected from electron paramagnetic resonance (NMR), mass spectrometry (MS), nuclear magnetic resonance (NMR), and isothermal titration calorimetry (ITC).

A recently accepted publication by Heffern and coworkers in Inorganic Chemistry identifies the copper(II) and zinc(II) binding site on a peptide hormone known as C-peptide. C-peptide is made alongside insulin in the pancreas and may help with kidney and blood vessel damage in patients with diabetes. Their findings show that copper(II) and zinc(II) share the same site and compete with each other for binding at the N-terminus of the peptide. In conjunction with their previous findings where copper(II) inhibits C-peptide action on kidney cells but zinc(II) does not, these observations expand our understanding of how metals may influence peptide hormone activity and provide a framework for future investigations.

More information at https://pubs.acs.org/doi/abs/10.1021/acs.inorgchem.0c01212