Figure 1.

Proline mutagenesis at position B28 of human insulin. a. Crystal structure of insulin (PDB 1MSO), highlighting ProB28 located at the dimer interface. b. Simplified scheme of insulin dissociation after injection. Insulin exists as a hexamer in the R state in the presence of zinc and phenolic ligands such as in the pharmaceutical formulation. After injection, insulin dissociates into lower-order oligomeric species that can diffuse more easily across the capillary membrane, enter the bloodstream, and bind to the insulin receptor. c. The structure of proline and the aliphatic proline analogs used in this study.