Please use this identifier to cite or link to this item: http://ahro.austin.org.au/austinjspui/handle/1/18575
Title: High Affinity Binding of Indium and Ruthenium Ions by Gastrins.
Authors: Baldwin, Graham S;George, Graham N;Pushie, M Jake
Affiliation: Molecular and Environmental Science Research Group Department of Geological Sciences, 114 Science Place, University of Saskatchewan, Saskatoon, S7N 5E2, Canada
Department of Surgery, Austin Health, The University of Melbourne, Heidelberg, Victoria, Australia
Issue Date: 12-Oct-2015
EDate: 2015
Citation: PloS one 2015; 10(10): e0140126
Abstract: The peptide hormone gastrin binds two ferric ions with high affinity, and iron binding is essential for the biological activity of non-amidated forms of the hormone. Since gastrins act as growth factors in gastrointestinal cancers, and as peptides labelled with Ga and In isotopes are increasingly used for cancer diagnosis, the ability of gastrins to bind other metal ions was investigated systematically by absorption spectroscopy. The coordination structures of the complexes were characterized by extended X-ray absorption fine structure (EXAFS) spectroscopy. Changes in the absorption of gastrin in the presence of increasing concentrations of Ga3+ were fitted by a 2 site model with dissociation constants (Kd) of 3.3 x 10-7 and 1.1 x 10-6 M. Although the absorption of gastrin did not change upon the addition of In3+ ions, the changes in absorbance on Fe3+ ion binding in the presence of indium ions were fitted by a 2 site model with Kd values for In3+ of 6.5 x 10-15 and 1.7 x 10-7 M. Similar results were obtained with Ru3+ ions, although the Kd values for Ru3+ of 2.6 x 10-13 and 1.2 x 10-5 M were slightly larger than observed for In3+. The structures determined by EXAFS all had metal:gastrin stoichiometries of 2:1 but, while the metal ions in the Fe, Ga and In complexes were bridged by a carboxylate and an oxygen with a metal-metal separation of 3.0-3.3 Å, the Ru complex clearly demonstrated a short range Ru-Ru separation, which was significantly shorter, at 2.4 Å, indicative of a metal-metal bond. We conclude that gastrin selectively binds two In3+ or Ru3+ ions, and that the affinity of the first site for In3+ or Ru3+ ions is higher than for ferric ions. Some of the metal ion-gastrin complexes may be useful for cancer diagnosis and therapy.
URI: http://ahro.austin.org.au/austinjspui/handle/1/18575
DOI: 10.1371/journal.pone.0140126
ORCID: 0000-0002-0944-8747
PubMed URL: 26457677
Type: Journal Article
Research Support, N.I.H., Extramural
Appears in Collections:Journal articles

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