Please use this identifier to cite or link to this item: http://hdl.handle.net/20.500.12779/5610
Title: The complex-formation behaviour of His residues in the fifth Cu2+ binding site of human Prion protein: a close look
Authors: M., Remelli
Valensin, Daniela 
D., Bacco
E., Gralka
R., Guerrini
Migliorini, Caterina
H., Kozlowski
Issue Date: 2009
Project: None 
Journal: NEW JOURNAL OF CHEMISTRY
Abstract: 
Human Prion Protein (hPrPC) is able to bind up to six Cu2+ ions. Four of them can be allocated in the ‘‘octarepeat domain’’, a region of the unstructured N-terminal domain containing four tandem-repetitions of the sequence PHGGGWGQ. It is widely accepted that the additional binding sites correspond to His-96 and His-111 residues. However, recent literature does not agree on the role and the behavior of these sites in Cu2+ complexation to hPrPC. In order to shed more light on this topic, some peptidic analogues of the PrP92–113 fragment were synthesized: (H96A)PrP92–113, (H111A)PrP92–113, (H96Nt-Me-His)PrP92–113, (H111Nt-Me-His)PrP92–113, (H96Nt-Me-His)PrP92–100, (H111Nt-Me-His)PrP106–113, where an alanine or a histidine methylated at the t nitrogen atom of its imidazole ring have been substituted to His-96 or His-111. The first two ligands allowed to confirm that His-111 binding site is stronger than His-96 one: they act as independent sites even at Cu2+ ion substoichiometric levels. Neither multihistidine binding nor bis-complex formation has been detected at neutral pH. Nt methylation gave evidence that t nitrogens of imidazole residues can participate in complex-formation only at acidic pH, where displacement of amidic protons by Cu2+ ions is not allowed. Finally, the length of the fragment does not appear to have any significant influence on the behavior of the two His-96 and His-111 binding sites, from the point of view of either the coordination geometry or their relative strength.
Description: 
26953
URI: http://hdl.handle.net/20.500.12779/5610
ISSN: 1144-0546
DOI: 10.1039/b9nj00202b
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