Anopheles gambiae, Anoga-HrTH hormone, free and bound structure-A nuclear magnetic resonance experiment

Grace Mugumbate, Graham E. Jackson, David Van Der Spoel, K. Kövér, László Szilágyi

Research output: Contribution to journalArticle

8 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)94-100
Number of pages7
JournalPeptides
Volume41
DOIs
Publication statusPublished - Mar 2013

Fingerprint

Anopheles gambiae
Molecular Dynamics Simulation
Insecticides
Culicidae
Neuropeptides
Malaria
Hydrogen
Magnetic Resonance Spectroscopy
Nuclear magnetic resonance
Hormones
Ligands
Membranes
Free energy
Conformations
Molecular dynamics
Hydrogen bonds
Crystal structure
Experiments
Molecules
adipokinetic hormone

Keywords

  • Anoga-HrTH
  • Anopheles gambiae
  • AUTODOCK
  • GROMACS
  • Molecular dynamics

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology
  • Physiology
  • Cellular and Molecular Neuroscience

Cite this

Anopheles gambiae, Anoga-HrTH hormone, free and bound structure-A nuclear magnetic resonance experiment. / Mugumbate, Grace; Jackson, Graham E.; Van Der Spoel, David; Kövér, K.; Szilágyi, László.

In: Peptides, Vol. 41, 03.2013, p. 94-100.

Research output: Contribution to journalArticle

Mugumbate, Grace ; Jackson, Graham E. ; Van Der Spoel, David ; Kövér, K. ; Szilágyi, László. / Anopheles gambiae, Anoga-HrTH hormone, free and bound structure-A nuclear magnetic resonance experiment. In: Peptides. 2013 ; Vol. 41. pp. 94-100.
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