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ESEEM analysis of multi-histidine Cu(II)-coordination in model complexes, peptides, and amyloid-β.

Silva KI, Michael BC, Geib SJ, Saxena S - J Phys Chem B (2014)

Bottom Line: We confirm that component II only contains single histidine coordination, using ESEEM and set of model complexes.The ESEEM experiments carried out on systematically (15)N-labeled peptides reveal that, in component II, His 13 and His 14 are more favored as equatorial ligands compared to His 6.Revealing molecular level details of subcomponents in metal ion coordination is critical in understanding the role of metal ions in Alzheimer's disease etiology.

View Article: PubMed Central - PubMed

Affiliation: Department of Chemistry, University of Pittsburgh , Pittsburgh, Pennsylvania 15260, United States.

ABSTRACT
We validate the use of ESEEM to predict the number of (14)N nuclei coupled to a Cu(II) ion by the use of model complexes and two small peptides with well-known Cu(II) coordination. We apply this method to gain new insight into less explored aspects of Cu(II) coordination in amyloid-β (Aβ). Aβ has two coordination modes of Cu(II) at physiological pH. A controversy has existed regarding the number of histidine residues coordinated to the Cu(II) ion in component II, which is dominant at high pH (∼8.7) values. Importantly, with an excess amount of Zn(II) ions, as is the case in brain tissues affected by Alzheimer's disease, component II becomes the dominant coordination mode, as Zn(II) selectively substitutes component I bound to Cu(II). We confirm that component II only contains single histidine coordination, using ESEEM and set of model complexes. The ESEEM experiments carried out on systematically (15)N-labeled peptides reveal that, in component II, His 13 and His 14 are more favored as equatorial ligands compared to His 6. Revealing molecular level details of subcomponents in metal ion coordination is critical in understanding the role of metal ions in Alzheimer's disease etiology.

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Comparison of ESEEM spectraof Cu(II)–DAHK complex and one-imidazolecomplex. Only one 14N-ESEEM active nuclei is present inthe reported coordination of DAHK.
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fig4: Comparison of ESEEM spectraof Cu(II)–DAHK complex and one-imidazolecomplex. Only one 14N-ESEEM active nuclei is present inthe reported coordination of DAHK.

Mentions: In order to test our claim in a biologicallyrelevant system, ESEEM experiments were conducted on two differentpeptide fragments with well-known Cu(II) coordination. The four aminoacid peptide DAHK is the N-terminus fragment of the human serum albumin.56 In the DAHK peptide, the imidazole ring of thehistidine residue coordinates to the Cu(II) ion, and the distal nitrogenof the imidazole ring is the only ESEEM active nuclei as shown inFigure 4. The comparison between the ESEEMspectra of Cu(II)–DAHK and one-imidazole complex is shown inFigure 4. Both complexes show the characteristicthree NQI peaks and the broad DQ peak. The intensities of the DQ peaksare comparable in the two complexes. The intensity of DQ peak reflectsthe number of imidazoles coordinated to the Cu(II) center.61 The normalized integrated intensity for Cu(II)–DAHKis 7.0 ± 0.1 compared to 8.4 ± 0.1 for the one-imidazolecomplex (Table 1).


ESEEM analysis of multi-histidine Cu(II)-coordination in model complexes, peptides, and amyloid-β.

Silva KI, Michael BC, Geib SJ, Saxena S - J Phys Chem B (2014)

Comparison of ESEEM spectraof Cu(II)–DAHK complex and one-imidazolecomplex. Only one 14N-ESEEM active nuclei is present inthe reported coordination of DAHK.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4120975&req=5

fig4: Comparison of ESEEM spectraof Cu(II)–DAHK complex and one-imidazolecomplex. Only one 14N-ESEEM active nuclei is present inthe reported coordination of DAHK.
Mentions: In order to test our claim in a biologicallyrelevant system, ESEEM experiments were conducted on two differentpeptide fragments with well-known Cu(II) coordination. The four aminoacid peptide DAHK is the N-terminus fragment of the human serum albumin.56 In the DAHK peptide, the imidazole ring of thehistidine residue coordinates to the Cu(II) ion, and the distal nitrogenof the imidazole ring is the only ESEEM active nuclei as shown inFigure 4. The comparison between the ESEEMspectra of Cu(II)–DAHK and one-imidazole complex is shown inFigure 4. Both complexes show the characteristicthree NQI peaks and the broad DQ peak. The intensities of the DQ peaksare comparable in the two complexes. The intensity of DQ peak reflectsthe number of imidazoles coordinated to the Cu(II) center.61 The normalized integrated intensity for Cu(II)–DAHKis 7.0 ± 0.1 compared to 8.4 ± 0.1 for the one-imidazolecomplex (Table 1).

Bottom Line: We confirm that component II only contains single histidine coordination, using ESEEM and set of model complexes.The ESEEM experiments carried out on systematically (15)N-labeled peptides reveal that, in component II, His 13 and His 14 are more favored as equatorial ligands compared to His 6.Revealing molecular level details of subcomponents in metal ion coordination is critical in understanding the role of metal ions in Alzheimer's disease etiology.

View Article: PubMed Central - PubMed

Affiliation: Department of Chemistry, University of Pittsburgh , Pittsburgh, Pennsylvania 15260, United States.

ABSTRACT
We validate the use of ESEEM to predict the number of (14)N nuclei coupled to a Cu(II) ion by the use of model complexes and two small peptides with well-known Cu(II) coordination. We apply this method to gain new insight into less explored aspects of Cu(II) coordination in amyloid-β (Aβ). Aβ has two coordination modes of Cu(II) at physiological pH. A controversy has existed regarding the number of histidine residues coordinated to the Cu(II) ion in component II, which is dominant at high pH (∼8.7) values. Importantly, with an excess amount of Zn(II) ions, as is the case in brain tissues affected by Alzheimer's disease, component II becomes the dominant coordination mode, as Zn(II) selectively substitutes component I bound to Cu(II). We confirm that component II only contains single histidine coordination, using ESEEM and set of model complexes. The ESEEM experiments carried out on systematically (15)N-labeled peptides reveal that, in component II, His 13 and His 14 are more favored as equatorial ligands compared to His 6. Revealing molecular level details of subcomponents in metal ion coordination is critical in understanding the role of metal ions in Alzheimer's disease etiology.

Show MeSH
Related in: MedlinePlus