Comparison of active conformations of the insectatachykinin/tachykinin and insect kinin/Tyr-W-MIF-1 neuropeptide family pairs

Ann N Y Acad Sci. 1999;897:388-400. doi: 10.1111/j.1749-6632.1999.tb07908.x.

Abstract

A comparison of solution conformations of active, restricted-conformation analogues of two sequence-similar insect/vertebrate neuropeptide family pairs shed light on the potential existence of molecular evolutionary relationships. Analogues of the locustatachykinins and the mammalian tachykinin substance P, containing a sterically hindered Aib-NMePhe/Tyr residue block, share similar low-energy turn conformations incorporating a cis peptide bond. Conversely, restricted conformation analogues of the insect kinins and the mammalian opiate peptide Tyr-W-MIF-1, with near identical C-terminal tetrapeptide sequences, adopt different conformations. The insect kinins adopt a cisPro 1-4 beta-turn, in which the Phe1 is critical for bioactivity. Tyr-W-MIF-1 prefers a transPro 2-5 turn, and an additional N-terminal Phe severely inhibits mu-opiate receptor binding. Comparisons of the chemical/conformational requirements for receptor interaction are consistent with a distant evolutionary relationship between the insectatachykinins and tachykinins, but not between the insect kinins and Tyr-W-MIF-1. Therefore, analogues of the insect kinins with pest control potential can be readily designed to avoid mammalian interactions.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Humans
  • Insecta*
  • MSH Release-Inhibiting Hormone / analogs & derivatives
  • MSH Release-Inhibiting Hormone / chemistry
  • MSH Release-Inhibiting Hormone / physiology
  • Mammals
  • Models, Molecular
  • Narcotic Antagonists / chemistry
  • Neuropeptides / chemistry*
  • Neuropeptides / physiology
  • Protein Conformation
  • Tachykinins / chemistry*
  • Tachykinins / physiology

Substances

  • Narcotic Antagonists
  • Neuropeptides
  • Tachykinins
  • tyrosyl-prolyl-tryptophyl-glycinamide
  • MSH Release-Inhibiting Hormone