First studies on the interactions of the C-terminal cystatin C fragment 85-94 with Cu(II) ions

Aneta Szymańska , Aleksandra Marciniak , Edward Krzyżak , Justyna Brasuń

Abstract

The hypothesis connecting dyshomeostasis of selected metal ions in the brain with increased probability of the development of severe neurodegenerative diseases is gaining increasing attention. The mechanisms of metal toxicity can be studied using different methodologies. One of the approaches is based on peptides as mimetics of the metal binding sites in proteins. In our studies, we have focused on human cystatin C (hCC) as one of the proteins involved in neurodegeneration. Physiologically, it is an important inhibitor of cysteine proteases and modulator of many physiological and pathological states. Native hCC is present at particularly high concentrations in cerebrospinal fluid (CSF) and was shown to possess both neurodegenerative and neuroprotective propensities. We have studied the copper(II) binding to its C-terminal fragment containing two histidine residues as potential site(s) for metal coordination. Our data indicate that the hCC fragment is fully capable of effective metal binding. Moreover, two potential metal binding sites can be proposed for the studied ligand. At the physiological range of pH formation of two types of complexes was observed: with imidazole and one/two amide donors in the coordination sphere of the metal ion and the final species characterized by the 4N-type of coordination.
Author Aneta Szymańska (FCh / DBCh / LMCh)
Aneta Szymańska,,
- Laboratory of Medical Chemistry
, Aleksandra Marciniak
Aleksandra Marciniak,,
-
, Edward Krzyżak
Edward Krzyżak,,
-
, Justyna Brasuń
Justyna Brasuń,,
-
Journal seriesJournal of Coordination Chemistry, ISSN 0095-8972, (A 25 pkt)
Issue year2019
Vol72
No9
Pages1592-1602
Publication size in sheets0.5
Keywords in EnglishCystatin C, N ligands, copper, potentiometric studies, spectroscopic studies
ASJC Classification2505 Materials Chemistry; 1606 Physical and Theoretical Chemistry
DOIDOI:10.1080/00958972.2019.1605065
Languageen angielski
Score (nominal)25
ScoreMinisterial score = 20.0, 16-07-2019, ArticleFromJournal
Ministerial score (2013-2016) = 25.0, 16-07-2019, ArticleFromJournal
Publication indicators Scopus SNIP (Source Normalised Impact per Paper): 2016 = 0.511; WoS Impact Factor: 2017 = 1.703 (2) - 2017=1.39 (5)
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