Structural analysis and sheep pituitary receptor binding of GnRH and its complexes with metal ions

J Inorg Biochem. 2003 Feb 1;94(1-2):28-35. doi: 10.1016/s0162-0134(02)00630-x.

Abstract

Binding of GnRH and its metal complexes to a sheep pituitary receptor have been investigated showing that Cu(II)-GnRH complex is more effectively bound to the receptor than the metal-free ligand, while Ni(II) and Co(II) complexes are less effective than the metal-free GnRH. Earlier studies have explained reasonably well the complex formation with cupric ion, while in this work extensive 1H NMR measurements have been performed for free gonadotropin-releasing hormone (GnRH) and its complexes with Ni(II) in DMSO (dimethyl sulfoxide) solution. This study shows the high order of organization of the metal-free peptide in DMSO solution with two structured 'domains' whose relative orientation is modulated by the mobility of the central glycine. Furthermore, theoretical calculations were performed for the Ni(II)-GnRH complex. The data obtained in this work supports previous studies on the co-ordination of Ni(II) ions with GnRH in aqueous solutions at high pH [J. Inorg. Biochem. 33 (1988) 11] and suggest an experimental procedure to reproduce high pH in DMSO solution. In the Ni(II) complex, the metal ion was found to co-ordinate with four nitrogen atoms inducing a well definite arrangement of aromatic side-chains and a rigid backbone structure.

MeSH terms

  • Animals
  • Gonadotropin-Releasing Hormone / metabolism*
  • Metals / metabolism*
  • Nuclear Magnetic Resonance, Biomolecular
  • Pituitary Gland / metabolism*
  • Protein Binding
  • Receptors, LHRH / metabolism*
  • Sheep

Substances

  • Metals
  • Receptors, LHRH
  • Gonadotropin-Releasing Hormone