Stereospecific interactions of proline residues in protein structures and complexes

Abstract

The constrained backbone torsion angle of a proline (Pro) residue has usually been invoked to explain its three-dimensional context in proteins. Here we show that specific interactions involving the pyrrolidine ring atoms also contribute to its location in a given secondary structure and its binding to another molecule. It is adept at participating in two rather non-conventional interactions, C-H...Πand C-H...O. The geometry of interaction between the pyrrolidine and aromatic rings, vis-a-vis the occurrence of the C-H...Π interactions has been elucidated. Some of the secondary structural elements stabilized by Pro-aromatic interactions are β-turns, where a Pro can interact with an adjacent aromatic residue, and in antiparallel β-sheet, where a Pro in an edge strand can interact with an aromatic residue in the adjacent strand at a non-hydrogen-bonded site. The C-H groups at the C^α and C^δ; positions can form strong C-H...O interactions (as seen from the clustering of points) and such interactions involving a Pro residue at C' position relative to an α-helix can cap the hydrogen bond forming potentials of the free carbonyl groups at the helix C terminus. Functionally important Pro residues occurring at the binding site of a protein almost invariably engage aromatic residues (with one of them being held by C-H...Π interaction) from the partner molecule in the complex, and such aromatic residues are highly conserved during evolution.