The three‐dimensional similarity between a dimeric antiparallel extended structure and a β‐turn folded form of enkephalin

Abstract

The three-dimensional similarity between two fundamental conformations, a dimeric antiparallel extended structure and a type I' p-turn folded form, of enkephalin was examined by computer graphic and empirical energy calculation methods. By the rotation of Tyr and Phe side chains, one half of the former structure could mimic the three-dimensional form of the latter without a large loss of conformational energy. This result provides a new idea for considering the conformation of enkephalin suitable for the multiple opioid receptors. The active conformation of enkephalin for ,u-and S-opioid receptors is discussed in the light of the present study.

Importance of folded monomer and extended antiparallel dimer structures as enkephalin active conformation Molecular dynamics simulations of [Met5]enkephalin in water

“…Accordingly, this result can account for the conflicting conclusions presented in previous solution studies on the stable conformation of enkephalins [14]. This paper further indicates a biological implication for the discussion on enkephalin monomer and dimer structures with respect to the opioid receptor multiplicity [4,5,8,11,16,17].…”

“…Nevertheless, our previous studies [8,10,11] have pointed to the importance of the dimer structure as a biologically active conformation.…”

Conformational analysis of an active chemotactic peptide analog containing z-dehydrophbnylalanine at position 3

“…multiple receptor sites could recognize discrete peptide conformations as in the well documented case of the enkephalins21. The possibility of similarity of the atoms interacting with the receptor, for both folded and extended structures may a150 be a factor as noted recently for enkephalins 22 .…”

Cross‐checking of nanoelectrospray ionization mass spectrometry and computer simulation for the evaluation of the interaction strength of non‐covalently bound enkephalins in solution

“…The basic strategy we employed in this study was as follows: the initial coordinates of the dimer complexes of the optical isomers of LE were chosen so that they had main‐chain and side‐chain conformations identical with those of the LE dimer complex except the chirality of corresponding amino acid(s). Similarly, the initial coordinates of the monomers of LE and its optical isomers were chosen so that they had main‐chain and side‐chain conformations similar to those of the corresponding dimer complexes 30–32. The local energy minima thus obtained for LE and its optical isomers may reflect the effect of the chirality difference, being relatively free from fortuity in the selection of the initial coordinates.…”