Structural studies of adipokinetic hormones in water and DPC micelle solution using NMR distance restrained molecular dynamics.
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 β-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 β-turn facing the surface. Declu-CC interacts more strongly with the β-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.
Department of Chemistry, University of Cape Town, Private Bag, Rondebosch, Cape Town 7701, South Africa. Electronic address: Graham.Jackson@uct.ac.za.
Graham E
GE
Jackson
Department of Chemistry, University of Cape Town, Private Bag, Rondebosch, Cape Town 7701, South Africa.
Riedaa
R
Gamieldien
Department of Chemistry, University of Cape Town, Private Bag, Rondebosch, Cape Town 7701, South Africa.
Grace
G
Mugumbate
Biological Sciences, University of Cape Town, Private Bag, Rondebosch, Cape Town 7701, South Africa.
Gerd
G
Gäde
D001681:Biological Assay / Q000379:methods*; D007301:Insect Hormones / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D008823:Micelles; D056004:Molecular Dynamics Simulation; D009842:Oligopeptides / Q000737:chemistry*; D010767:Phosphorylcholine / Q000031:analogs & derivatives* / Q000737:chemistry; D017434:Protein Structure, Tertiary; D011761:Pyrrolidonecarboxylic Acid / Q000031:analogs & derivatives* / Q000737:chemistry; D014867:Water / Q000737:chemistry*
D007301:Insect Hormones; D008823:Micelles; D009842:Oligopeptides; C044833:adipokinetic hormone; D014867:Water; D010767:Phosphorylcholine; C028810:dodecylphosphocholine; D011761:Pyrrolidonecarboxylic Acid
Adipokinetic hormones (AKHs); Declu-CC; Melme-CC; Molecular dynamics simulations and receptor docking