Title: | Active conformation of an insect neuropeptide family |
Author(s): | Nachman RJ; Roberts VA; Dyson HJ; Holman GM; Tainer JA; |
Address: | "Veterinary Toxicology and Entomology Research Laboratory, U.S. Department of Agriculture, College Station, TX 77840" |
ISSN/ISBN: | 0027-8424 (Print) 1091-6490 (Electronic) 0027-8424 (Linking) |
Abstract: | "To understand the structural and chemical basis for insect neuropeptide activity, we have designed, synthesized, and determined the conformation of a biologically active cyclic analog of the pyrokinins, an insect neuropeptide family that mediates myotropic (visceral muscle contractile) activity. Members of this insect neuropeptide family share the common C-terminal pentapeptide sequence Phe-Xaa-Pro-Arg-Leu-NH2 (Xaa = Ser, Thr, or Val). Circular dichroic, nuclear magnetic resonance, and molecular dynamics analyses of the conformationally restricted cyclic pyrokinin analog cyclo(-Asn-Thr-Ser-Phe-Thr-Pro-Arg-Leu-) indicated the presence of a beta-turn in the active core region encompassing residues Thr-Pro-Arg-Leu. The rigid cyclic analog retains biological activity, suggesting that its C-terminal beta-turn is the active pyrokinin conformation recognized by the myotropic receptor. As individual pyrokinins and pyrokinin-like neuropeptides demonstrate both oviduct-contractile and pheromone-biosynthesis activities in various insects, the biologically active beta-turn structure reported here holds broad significance for many biological processes" |
Keywords: | "Amino Acid Sequence Animals Circular Dichroism Cockroaches/*analysis Magnetic Resonance Spectroscopy Molecular Sequence Data Molecular Structure Neuropeptides/chemical synthesis/*chemistry Peptides, Cyclic/chemical synthesis/*chemistry Protein Conformatio;" |
Notes: | "MedlineNachman, R J Roberts, V A Dyson, H J Holman, G M Tainer, J A eng Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. 1991/05/15 Proc Natl Acad Sci U S A. 1991 May 15; 88(10):4518-22. doi: 10.1073/pnas.88.10.4518" |