Conformational study of insect adipokinetic hormones using NMR constrainedmolecular dynamics

Mem-CC (pGlu-Leu-Asn-Tyr-Ser-Pro-Asp-Trp-NH2), Tem-HrTH (pGlu-Leu-Asn-Phe-S er-Pro-Asn-Trp-NH2) and Del-CC (pGlu-Leu-Asn-Phe-Ser-Pro-Asn-Trp-Gly-Asn-NH 2) are adipokinetic hormones, isolated from the corpora cardiaca of differe nt insect species. These hormones regulate energy metabolism during flight and so are intimately involved in an insect's mobility. Secondary structura l elements of these peptides and the N7 analogue, [N7]-Mem-CC (pGlu-Leu-Asn -Tyr-Ser-Pro-Asn-Trp-NH2), have been determined in dimethylsulfoxide soluti on using NMR restrained molecular mechanic simulations. The neuropeptides w ere all found to have an extended structure for the first 4 residues and a beta -turn between residues 4-8. For Tem-HrTH and Del-CC, asparagine (N7) w hich is postulated to be involved in receptor binding and/or activation, pr ojects outward form the beta -turn. Mem-CC does not have an asparagine at p osition 7 while, for [N7]-Mem-CC, the N7 sidechain folds inside the beta -t urn preventing its interaction with the receptor.