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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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CW-ESR spectra of model complexes.
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fig2: CW-ESR spectra of model complexes.

Mentions: First, CW-ESR experiments were carriedout on the model complexes. As shown in Figure 2, the one-imidazole complex has g∥ and A∥ values of (2.22 ±0.005) and (191 ± 1) Gauss, respectively. These ESR parameterscorrespond to four nitrogen nuclei coordinated to the Cu(II) centerin the equatorial plane,59 which is consistentwith the structure of the one-imidazole complex, as shown in Figure 1a. The two-imidazole complex has g∥ and A∥ valuesof (2.30 ± 0.005) and (158 ± 1) Gauss, respectively, whichis consistent with a two nitrogen and two oxygen nuclei equatorialcoordination.59 For the four-imidazolecomplex, g∥ and A∥ values are (2.26 ± 0.005) and (182 ±1) Gauss, respectively, which again is consistent for four directlycoordinated nitrogen nuclei.59 Hence, CW-ESRparameters clearly show that model complexes maintain the same Cu(II)coordination environment in solution.


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)

CW-ESR spectra of model complexes.
© Copyright Policy
Related In: Results  -  Collection

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

fig2: CW-ESR spectra of model complexes.
Mentions: First, CW-ESR experiments were carriedout on the model complexes. As shown in Figure 2, the one-imidazole complex has g∥ and A∥ values of (2.22 ±0.005) and (191 ± 1) Gauss, respectively. These ESR parameterscorrespond to four nitrogen nuclei coordinated to the Cu(II) centerin the equatorial plane,59 which is consistentwith the structure of the one-imidazole complex, as shown in Figure 1a. The two-imidazole complex has g∥ and A∥ valuesof (2.30 ± 0.005) and (158 ± 1) Gauss, respectively, whichis consistent with a two nitrogen and two oxygen nuclei equatorialcoordination.59 For the four-imidazolecomplex, g∥ and A∥ values are (2.26 ± 0.005) and (182 ±1) Gauss, respectively, which again is consistent for four directlycoordinated nitrogen nuclei.59 Hence, CW-ESRparameters clearly show that model complexes maintain the same Cu(II)coordination environment in solution.

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