CuII binding sites located at His-96 and His-111 of the human prion protein: thermodynamic and spectroscopic studies on model peptides
| Autor: | Elena Gaggelli, Carolina Gajda, Henryk Kozlowski, Daniela Valensin, Remo Guerrini, Rafał Nadolny, Wojciech Kamysz, Gianni Valensin, Elena Porciatti, Maurizio Remelli, Dimitri Bacco, Ewa Gralka |
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| Rok vydání: | 2008 |
| Předmět: |
Models
Molecular Magnetic Resonance Spectroscopy Prions Potentiometric titration Molecular Conformation complex-formation equilibria Calorimetry Prion Protein Ring (chemistry) Ligands Inorganic Chemistry Residue (chemistry) chemistry.chemical_compound Amide Imidazole Histidine Binding site Peptide sequence His-peptides Oligopeptide Binding Sites Circular Dichroism Electron Spin Resonance Spectroscopy solution studies NMR potentiometry calorimetry copper(II)-peptide binding neurotoxic peptide Crystallography chemistry Potentiometry Thermodynamics Spectrophotometry Ultraviolet Protons Peptides Copper |
| Zdroj: | Dalton transactions (Cambridge, England : 2003). (38) |
| ISSN: | 1477-9226 |
| Popis: | The prion protein (PrP) is a Cu(2+)-binding cell-surface glycoprotein. Using PrP peptide fragments, by means of potentiometric, spectroscopic and thermodynamic techniques, we have shown that Cu(2+) ions bind to the region comprising His-96, His-111 and the octarepeat domain within residues 60-91. Cu(2+) may bind in different modes, which strongly depend both on His position within the peptide sequence and on the adjacent residues. We have used a series of protected oligopeptides having His at the C- or the N-terminus, inducing different binding modes to amide nitrogens around the His residue, either towards the N- or C-terminus. His imidazole acts as an anchoring site for Cu(2+) and then binding to ionized amide nitrogens follows. When it is directed towards the C-terminus the formation of a less stable seven-membered chelate ring with a {N(im), N(-)} binding mode occurs. When coordination goes towards the N-terminus the thermodynamically more stable six-membered chelate ring is formed. NMR data suggest that both the coordination modes are possible for the model peptides; however, the thermodynamic measurements show that they only slightly differ in energy and the influence of the adjacent amino acid residues can address the coordination toward the C- or the N-terminus. |
| Databáze: | OpenAIRE |
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