[NMR paper] Structural studies of adipokinetic hormones in water and DPC micelle solution using NMR distance restrained molecular dynamics.

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Structural studies of adipokinetic hormones in water and DPC micelle solution using NMR distance restrained molecular dynamics.

Related Articles Structural studies of adipokinetic hormones in water and DPC micelle solution using NMR distance restrained molecular dynamics.

Peptides. 2014 Mar;53:270-7

Authors: Jackson GE, Gamieldien R, Mugumbate G, Gäde G

Abstract
Melme-CC (pGlu-Leu-Asn-Tyr-Ser-Pro-Asp-Trp amide) and Declu-CC (pGlu-Leu-Asn-Phe-Ser-Pro-Asn-Trp-Gly-Asn amide) are members of the insect adipokinetic hormone family with very different activities in the locust bioassay. The conformations of both peptides were determined in water and in a phospholipid (DPC) micelle solution using nuclear magnetic resonance (NMR) restrained molecular dynamics simulations. In water, Melme-CC has one dominant conformation while in DPC solution it has two preferred conformation. In water, Declu-CC has two conformations but in DPC solution it has one preferred conformation, which is similar to one of the water conformations. All the conformations have type IV ?-turn between residues 4 and 7. The binding of the two peptides to the DPC micelle is different. Melme-CC does not bind strongly to the surface and is oriented with the ?-turn facing the surface. Declu-CC interacts more strongly with the ?-turn facing away from the surface. Both termini having hydrophobic interactions with the surface. In Declu-CC the side chain of Asn(7) projects away from the chain while in Melme-CC the Asp(7) side chain is folded inside the chain. The different orientation of these side chains may account for the much higher biological activity of Declu-CC in mobilizing lipids in the locust compared to the poor biological effect of Melme-CC in this bioassay. Receptor binding of Declu-CC was tested using a model AKH receptor from Anopheles gambiae. A free energy of binding of -38.5 kJ mol(-1) was found.


PMID: 24444447 [PubMed - indexed for MEDLINE]



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