Comparison of active conformations of the insectatachykinin/tachykinin and insect kinin/Tyr-W-MIF-1 neuropeptide family pairs.
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.
Nachman
R J
RJ
VERU/SPARC, United States Department of Agriculture, College Station, Texas 77845, USA. nachman@acs.tamu.edu
Moyna
G
G
Williams
H J
HJ
Zabrocki
J
J
Zadina
J E
JE
Coast
G M
GM
Varden Broeck
J
J
D000595:Amino Acid Sequence; D000818:Animals; D006801:Humans; D007313:Insecta; D009075:MSH Release-Inhibiting Hormone / Q000031:analogs & derivatives / Q000737:chemistry / Q000502:physiology; D008322:Mammals; D008958:Models, Molecular; D009292:Narcotic Antagonists / Q000737:chemistry; D009479:Neuropeptides / Q000737:chemistry* / Q000502:physiology; D011487:Protein Conformation; D015320:Tachykinins / Q000737:chemistry* / Q000502:physiology
D009292:Narcotic Antagonists; D009479:Neuropeptides; D015320:Tachykinins; C077532:tyrosyl-prolyl-tryptophyl-glycinamide; D009075:MSH Release-Inhibiting Hormone