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Structural and Dynamic Characterization of Copper(II) Binding of the Human Prion Protein Outside the Octarepeat Region
Author(s) -
Berti Francesco,
Gaggelli Elena,
Guerrini Remo,
Janicka Anna,
Kozlowski Henryk,
Legowska Anna,
Miecznikowska Hanna,
Migliorini Caterina,
Pogni Rebecca,
Remelli Maurizio,
Rolka Krzysztof,
Valensin Daniela,
Valensin Gianni
Publication year - 2007
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.200601225
Subject(s) - electron paramagnetic resonance , copper , spectroscopy , nuclear magnetic resonance spectroscopy , chemistry , metal , crystallography , characterization (materials science) , binding site , molecular dynamics , coordination sphere , nuclear magnetic resonance , materials science , stereochemistry , computational chemistry , biochemistry , crystal structure , organic chemistry , nanotechnology , physics , quantum mechanics
Human prion protein (hPrP) fragments encompassing the 91–120 region, namely hPrP92–100 (SP1), hPrP106–113 (SP2), hPrP91–120 (LP1), and hPrP91–114 (LP2), were considered for delineation of the Cu II ‐binding site(s). NMR and EPR spectroscopy results obtained from LP1 or LP2 were compared with those obtained from SP1 and SP2. The coexistence of two binding sites, one centered at His96 and the other at His111, was evidenced and ratified by ESI mass spectrometry at low and high metal:peptide ratios. While room‐temperature NMR spectroscopy data were consistent with the binding site centered on His111 being approximately fourfold stronger than that centered on His96, low‐temperature EPR spectroscopy results yielded evidence for the opposite trend. This disagreement, which has also occurred in the literature, was clarified by temperature‐dependent molecular dynamics runs that demonstrated Met112 approaching the metal at room temperature, a process that is expected to stabilize the His111‐centered binding site through hydrophobic shielding of the metal coordination sphere.