دورية أكاديمية
أعرض في EDS

Structural Insight into Redox Dynamics of Copper Bound N-Truncated Amyloid-β Peptides from in Situ X-ray Absorption Spectroscopy.

التفاصيل البيبلوغرافية
العنوان: Structural Insight into Redox Dynamics of Copper Bound N-Truncated Amyloid-β Peptides from in Situ X-ray Absorption Spectroscopy.
المؤلفون: Streltsov VA; Florey Department of Neuroscience and Mental Health , The University of Melbourne , Melbourne , Australia.; School of Physics , The University of Melbourne , Melbourne , Australia., Ekanayake RSK; School of Physics , The University of Melbourne , Melbourne , Australia., Drew SC; Department of Medicine (Royal Melbourne Hospital) , The University of Melbourne , Melbourne , Australia., Chantler CT; School of Physics , The University of Melbourne , Melbourne , Australia., Best SP; School of Chemistry , The University of Melbourne , Melbourne , Australia.
المصدر: Inorganic chemistry [Inorg Chem] 2018 Sep 17; Vol. 57 (18), pp. 11422-11435. Date of Electronic Publication: 2018 Aug 31.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: American Chemical Society Country of Publication: United States NLM ID: 0366543 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1520-510X (Electronic) Linking ISSN: 00201669 NLM ISO Abbreviation: Inorg Chem Subsets: MEDLINE
أسماء مطبوعة: Original Publication: [Easton, Pa.] American Chemical Society.
مواضيع طبية MeSH: Amyloid beta-Peptides/*chemistry , Copper/*chemistry , Nitrogen/*chemistry, Amitriptyline ; Binding Sites ; Cryobiology ; Models, Molecular ; Oxidation-Reduction ; X-Ray Absorption Spectroscopy
مستخلص: X-ray absorption spectroscopy of Cu II amyloid-β peptide (Aβ) under in situ electrochemical control (XAS-EC) has allowed elucidation of the redox properties of Cu II bound to truncated peptide forms. The Cu binding environment is significantly different for the Aβ 1-16 and the N-truncated Aβ 4-9 , Aβ 4-12 , and Aβ 4-16 (Aβ 4-9/12/16 ) peptides, where the N-truncated sequence (F 4 R 5 H 6 ) provides the high-affinity amino-terminal copper nickel (ATCUN) binding motif. Low temperature (ca. 10 K) XAS measurements show the adoption of identical Cu II ATCUN-type binding sites (Cu II ATCUN ) by the first three amino acids (FRH) and a longer-range interaction modeled as an oxygen donor ligand, most likely water, to give a tetragonal pyramid geometry in the Aβ 4-9/12/16 peptides not previously reported. Both XAS-EC and EPR measurements show that Cu II :Aβ 4-16 can be reduced at mildly reducing potentials, similar to that of Cu II :Aβ 1-16 . Reduction of peptides lacking the H 13 H 14 residues, Cu II :Aβ 4-9/12 , require far more forcing conditions, with metallic copper the only metal-based reduction product. The observations suggest that reduction of Cu II ATCUN species at mild potentials is possible, although the rate of reduction is significantly enhanced by involvement of H 13 H 14 . XAS-EC analysis reveals that, following reduction, the peptide acts as a terdentate ligand to Cu I (H 13 , H 14 together with the linking amide oxygen atom). Modeling of the EXAFS is most consistent with coordination of an additional water oxygen atom to give a quasi-tetrahedral geometry. XAS-EC analysis of oxidized Cu II :Aβ 4-12/16 gives structural parameters consistent with crystallographic data for a five-coordinate Cu III complex and the Cu II ATCUN complex. The structural results suggest that Cu II and the oxidation product are both accommodated in an ATCUN-like binding site.
المشرفين على المادة: 0 (Amyloid beta-Peptides)
1806D8D52K (Amitriptyline)
789U1901C5 (Copper)
N762921K75 (Nitrogen)
تواريخ الأحداث: Date Created: 20180901 Date Completed: 20181011 Latest Revision: 20181011
رمز التحديث: 20240628
DOI: 10.1021/acs.inorgchem.8b01255
PMID: 30169035
قاعدة البيانات: MEDLINE
الوصف
تدمد:1520-510X
DOI:10.1021/acs.inorgchem.8b01255