Islet Amyloid Polypeptide (IAPP) is a hormone co-secreted with insulin and zinc from pancreatic β-cells. To overcome the low solubility of human IAPP, we characterized the zinc complexes species formed with: i) a mutated form of rat-IAPP(1-37;R18H) able to mimic the human IAPP; ii) the r-IAPP(1-37) and the IAPP(1-8) fragment. Stoichiometry, speciation and coordination features of zinc(II) complexes were unveiled by ESI-MS, potentiometric and NMR-based measurements combined with DFT and free-energy simulations. Mononuclear species start to form around pH 6; Zn 2+ binds both His18 and N-amino terminus in rat-IAPP(1-37; R18H).The in silico study allows us to assess not only a structured turn compact domain in r-IAPP(1-37) and r-IAPP(1-37;R18H) featured by a different free energy barrier for the transition from the compact to elongated conformation upon the coordination of Zn 2+  but also to bring into light a coordination shell further stabilized by non-covalent interactions.

Zinc interactions with a soluble mutated rat amylin to mimic whole human amylin. An experimental and simulation approach to understand stoichiometry, speciation and coordination of the metal complexes / Magrì, Antonio; Tabbì, Giovanni; Di Natale, Giuseppe; La Mendola, Diego; Pietropaolo, Adriana; Zoroddu, Maria Antonietta; Peana, Massimiliano; Rizzarelli, Enrico. - In: CHEMISTRY-A EUROPEAN JOURNAL. - ISSN 0947-6539. - (2020). [10.1002/chem.202002114]

Zinc interactions with a soluble mutated rat amylin to mimic whole human amylin. An experimental and simulation approach to understand stoichiometry, speciation and coordination of the metal complexes

Zoroddu, Maria Antonietta;Peana, Massimiliano;
2020

Abstract

Islet Amyloid Polypeptide (IAPP) is a hormone co-secreted with insulin and zinc from pancreatic β-cells. To overcome the low solubility of human IAPP, we characterized the zinc complexes species formed with: i) a mutated form of rat-IAPP(1-37;R18H) able to mimic the human IAPP; ii) the r-IAPP(1-37) and the IAPP(1-8) fragment. Stoichiometry, speciation and coordination features of zinc(II) complexes were unveiled by ESI-MS, potentiometric and NMR-based measurements combined with DFT and free-energy simulations. Mononuclear species start to form around pH 6; Zn 2+ binds both His18 and N-amino terminus in rat-IAPP(1-37; R18H).The in silico study allows us to assess not only a structured turn compact domain in r-IAPP(1-37) and r-IAPP(1-37;R18H) featured by a different free energy barrier for the transition from the compact to elongated conformation upon the coordination of Zn 2+  but also to bring into light a coordination shell further stabilized by non-covalent interactions.
Zinc interactions with a soluble mutated rat amylin to mimic whole human amylin. An experimental and simulation approach to understand stoichiometry, speciation and coordination of the metal complexes / Magrì, Antonio; Tabbì, Giovanni; Di Natale, Giuseppe; La Mendola, Diego; Pietropaolo, Adriana; Zoroddu, Maria Antonietta; Peana, Massimiliano; Rizzarelli, Enrico. - In: CHEMISTRY-A EUROPEAN JOURNAL. - ISSN 0947-6539. - (2020). [10.1002/chem.202002114]
File in questo prodotto:
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11388/234470
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 3
  • ???jsp.display-item.citation.isi??? 3
social impact