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1.  Effect of Common Buffers and Heterocyclic Ligands on the Binding of Cu(II) at the Multimetal Binding Site in Human Serum Albumin 
Visible-range circular dichroism titrations were used to study Cu(II) binding properties of Multimetal Binding Site (MBS) of Human Serum Albumin (HSA). The formation of ternary MBS-Cu(II)-Buffer complexes at pH 7.4 was positively verified for sodium phosphate, Tris, and Hepes, the three most common biochemical buffers. The phosphate > Hepes > Tris order of affinities, together with strong spectral changes induced specifically by Tris, indicates the presence of both Buffer-Cu(II) and Buffer-HSA interactions. All complexes are strong enough to yield a nearly 100% ternary complex formation in 0.5 mM HSA dissolved in 100 mM solutions of respective buffers. The effects of warfarin and ibuprofen, specific ligands of hydrophobic pockets I and II in HSA on the Cu(II) binding to MBS were also investigated. The effects of ibuprofen were negligible, but warfarin diminished the MBS affinity for Cu(II) by a factor of 20, as a result of indirect conformational effects. These results indicate that metal binding properties of MBS can be modulated directly and indirectly by small molecules.
doi:10.1155/2010/725153
PMCID: PMC2864911  PMID: 20467459
2.  Interactions of Zn(II) Ions with Three His-Containing Peptide Models of Histone H2A 
The interactions of Zn(ll) ions with the blocked hexapeptide models -TESHHK-, -TASHHK- and -TEAHHK- of the -ESHH- motif of the C-terminal of historic H2A were studied by using potentiometric and IH-NMR techniques. The first step of these studies was to compare the pKa values of the two His residues inside each hexapeptide calculated by potentiometric or H-NMR titrations. Hereafter, the potentiometric titrations in the pH range 5 11 suggest the formation of several monomeric Zn(ll) complexes. It was found that all hexapeptides bind to Zn(ll) ions initially through both imidazole nitrogens in weakly acidic and neutral solutions forming slightly distorted octahedral complexes. At higher pH values, the combination of potentiometric titrations and one and two dimensional NMR suggested no amide coordination in the coordination sphere of Zn(II) ions. Obviously, these studies support that the -ESHH- sequence of histone H2A is a potential binding site for Zn(II) ions similarly with the Cu(II) and Ni(ll) ions, presented in previous papers.
doi:10.1155/S1565363304000093
PMCID: PMC2267071  PMID: 18365073
3.  Studies of Zinc(II) and Nickel(II) Complexes of GSH, GSSG and Their Analogs Shed More Light on Their Biological Relevance 
Glutathione, Υ-Glu-Cys-Gly, is one of the most abundant small molecules in biosphere. Its main form is the reduced monomer (GSH), serving to detoxicate xenobiotics and heavy metals, reduce protein thiols, maintain cellular membranes and deactivate free radicals. Its oxidized dimer (GSSG) controls metal content of metallothionein. The results presented provided a quantitative and structural description of Zn(II)- glutathione complexes, including a novel ternary Zn(II)-GSH-His complex. A solution structure for this complex was obtained using 2D-NMR. The Complexes studied may contribute to both zinc and glutathione physiology. In the case of Ni(ll) complexes an interesting dependence of coordination modes on the ratios of reactants was found. At high GSH excess a Ni(GSH)2 complex is formed, with Ni(ll) bonded through S and N and/or O donor atoms. This complex may exist as a high- or low-spin species. Another goal of the studies presented was to describe the catalytic properties of Ni(II) ions towards GSH oxidation, which appeared to be an important step in nickel carcinogenesis. The pH dependence of oxidation rates allowed to determine the Ni(GSH)2 complex as the most active among the toxicologically relevant species. Protonation and oxidation of metal-free GSH and its analogues were also studied in detail. The monoprotonated form HL2- of GSH is the one most susceptible to oxidation, due to a salt bridge between S- and NH3+ groups, which activates the thiol.
doi:10.1155/S1565363304000172
PMCID: PMC2267084  PMID: 18365081

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