Interaction of the human prion PrP(106-126) sequence with copper(II), manganese(II), and zinc(II): NMR and EPR studies.

作者: Elena Gaggelli , Francesca Bernardi , Elena Molteni , Rebecca Pogni , Daniela Valensin

DOI: 10.1021/JA045958Z

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摘要: The synthetic peptide encompassing residues 106-126 (PrP106-126, KTNMKHMAGAAAAGAVVGGLG) of the human prion protein was considered for its binding properties toward copper(II), manganese(II) and zinc(II) at pH 5.7. 1H 13C 1D spectra, spin-lattice relaxation rates, 1H-15N 1H-13C HSQC 2D experiments were obtained in absence presence metal ions. While Zn(II) found to yield negligible effects upon any NMR parameter, metal-peptide association demonstrated by paramagnetic Cu(II) Mn(II) spectra. Delineation structures complexes sought interpreting effect on rates. Exchange molecules from coordination sphere shown provide sizable contribution observed Such calculated case Cu(II); whereas faster rates bound determining almost exclusively dominated exchange. Proton-metal distances therefore evaluated complex only used as restraints molecular dynamics calculations where structure obtained. bind copper through imidazole nitrogen ionized amide His-111 amino-terminal group with terminal carboxyl stabilizing ionic interactions. data interpreted demonstrate that hydrophobic C-terminal region not affecting copper-binding this tail is left free interact other target molecules. As Mn(II), qualitative information carbonyl oxygens Gly-124 Leu-125, beyond Gly-126 carboxyl, being close distance ion, also interacts, most likely, a hydrogen bond metal-bound water, ring His-111.

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