title: Anopheles gambiae, Anoga-HrTH hormone, free and bound structure--a nuclear magnetic resonance experiment.
abstract: The spread of malaria by the female mosquito, Anopheles gambiae, is dependent, amongst other things, on its ability to fly. This in turn, is dependent on the adipokinetic hormone, Anoga-HrTH (pGlu-Leu-Thr-Phe-Thr-Pro-Ala-Trp-NH2). No crystal structure of this important neuropeptide is available and hence NMR restrained molecular dynamics was used to investigate its conformational space in aqueous solution and when bound to a membrane surface. The results showed that Anoga-HrTH has an almost cyclic conformation that is stabilized by a hydrogen bond between the C-terminus and Thr3. Upon docking of the agonist to its receptor, this H-bond is broken and the molecule adopts a more extended structure. Preliminary AKHR docking calculations give the free energy of binding to be -47.30 kJ/mol. There is a close correspondence between the structure of the docked ligand and literature structure-activity studies. Information about the 3D structure and binding mode of Anoga-HrTH to its receptor is vital for the design of suitable mimetics which can act as insecticides.
authors: Department of Chemistry, University of Cape Town, Rondebosch, Cape Town, South Africa.
authors: Grace
authors: G
authors: Mugumbate
authors: Graham E
authors: GE
authors: Jackson
authors: David
authors: D
authors: van der Spoel
authors: Katalin E
authors: KE
authors: Kövér
authors: László
authors: L
authors: Szilágyi
mesh_terms: D000818:Animals; D000852:Anopheles; D001665:Binding Sites; D006860:Hydrogen Bonding; D007301:Insect Hormones / Q000737:chemistry*; D062105:Molecular Docking Simulation; D056004:Molecular Dynamics Simulation; D019906:Nuclear Magnetic Resonance, Biomolecular; D009842:Oligopeptides / Q000737:chemistry*; D011485:Protein Binding; D017433:Protein Structure, Secondary; D011761:Pyrrolidonecarboxylic Acid / Q000031:analogs & derivatives* / Q000737:chemistry; D011956:Receptors, Cell Surface / Q000737:chemistry; D013816:Thermodynamics
chemical_list: D007301:Insect Hormones; D009842:Oligopeptides; D011956:Receptors, Cell Surface; C044833:adipokinetic hormone; D011761:Pyrrolidonecarboxylic Acid