Three-dimensional analyses of the binding of synthetic chemotactic and opioid peptides in the Mcg light chain dimer.

Synthetic peptides with chemotactic or opioid activity were bound to crystals of a light chain dimer and their three-dimensional structures and modes of binding were determined by X-ray analysis. The chemotactic series consisted of di- and tripeptides initiated with N-formylmethionine or N-formylnorleucine residues. Opioid peptides included the enkephalins and casomorphins ranging in length from four to seven residues. The binding region of the protein proved to be malleable in adjusting to the surface contours of the peptides. Aromatic contact residues, as well as polypeptide segments of hypervariable loops, moved to improve the complementarity with the ligands. The peptides were even more flexible and tended to conform fairly closely to the space and geometry available for occupancy in the binding sites. Binding interactions were not confined to the interior of the cavity. In both the chemotactic and opioid series, the carboxyl tails of the peptides encroached upon the outer surfaces of the rim and contributed to the binding energies for the protein-ligand complexes. The peptide bond in N-formylmethionyltryptophan was found to be in the energetically unfavourable cis configuration. There was also evidence for less severe distortions in peptide bond geometry when N-formyltripeptides were bound to the dimer.