Crystal structures reveal that the sterically hindered pivaloyl-cisProlyl amide bond is energetically frustrated

CisPro/transPro isomerism at the prolyl amide bond is a fundamental dynamism governing protein folding, structure, and functions. Since cisPro crystal structures are rare, the interactions influencing their structures are less understood, unlike transPro. Crystal data for the sterically hindered pivaloyl-cisProlyl amide bond (2,2-dimethyl-1-(1-pyrrolidinyl)-1-propanone, Piv-cisPro) were particularly lacking for decades. Here we introduce Piv-Pro-Xaa-OMe dipeptides which crystallize with the elusive Piv-cisPro (Xaa is Leu/Ile) and the abundant Piv-transPro (Xaa is Gly/Phe) conformers.