Chiral Mutagenesis of Insulin

Insulin contains a structureofinsuliniswellcharacterized(3).IntheTstate,-turn (residues B20–B23) interposedbetween two receptor-binding elements, the central predominantconformationofthemonomerinsolution(4–6),-helixof the B chain (B9–B19) and its C-terminal -strand (B24–B28). The turn contains conserved glycines at B20 and B23.Although insulin exhibits marked conformational variabilityamong crystal forms, these glycines consistently maintainpositive dihedral angles within a classic type-I fide bridges required for its folding, stability, and function (5,-turn.Because the Ramachandran conformations of Gly