Cu2+ binding

Figure 18.15 (a) Cu2+ binding site in APP. (b) Proposed aggregation via a His bridge between two copper atoms to form a dimer. (From Curtain et al., 2001. Reproduced by permission of the Journal... 

To approach Cu2+binding to DNA from another direction the spectral change of the absorption spectra of [Cu(H20)6]2 1" was studied... 

Aronoff-Spencer E, Bums CS, Avdievich NI et al (2000) Identification of the Cu2+ binding sites in the N-terminal domain of the prion protein by EPR and CD spectroscopy. Biochemistry 39 13760-13771... 

Klewpatinond M, Davies P, Bowen S et al (2008) Deconvoluting the Cu2+ binding modes of full-length prion protein. J Biol Chem 283 1870-1881... 

EPR monitor for metal/protein interactions. Research on Cu2+ binding to PrP has been quite intensive (see below) which also included EPR experiments (see [80]). Most of these experiments were done on recombinant PrP or peptides derived from the N-terminus, especially from the octarepeat region. For further discussion on PrP metal binding site see next paragraph. 

On the other hand data reported in Fig. 8 Indicate that the higher charge-density of Xanthan compared to PS-10 shows up in a higher heat of Cu ion binding and in a lower activity coefficient of Na counterions. From the initial slope of the Qg against [Cu2tl /N plots of Fig. 6 one estimates for Xanthan in water a differential enthalpy of Cu2+ binding of about 1 Kcal per mole of copper bound. In conclusion, as found with the sulfated polysaccharides (Fig. 4) as well as with different synthetic poly-carboxylates ( ), chelation of Cu2+ ions by polyanions is a process systematically driven by the entropy. 

By comparing the level of the binding isotherms (figure 3) for both metals and pectins, it became possible to set up an affinity order of pectins, whatever their origin, for the five metal ions Cu2+ Pb + Zn2+ Ni2+ > Ca2+. This scale, already found by pH-measurements, confirmed that Cu2+ and Pb2+ were more strongly bound than the other thi cations with no difference between pectins. 

The formation constants of simple ligands such as F , Cl , and OH with the O-BISTREN complex (92) with two Cu(II) ions in it can be compared with the situation where these ligands bind to the free Cu2+ ion. 

The complex Cu(II)2(0-BISTREN) is much more acidic than the free Cu2+ ion, by a factor of more than three log units. This is primarily due to the presence of two Cu(II) ions, because the formation constant of the Cu2(OH)+ complex is not much less than that for the Cu2(0-BISTREN) complex with hydroxide. This is not a good indication of how well two free Cu2+ ions would bind hydroxide compared to the Cu2(0-BISTREN) complex, however, since one must take into account the dilution effect operative in the chelate effect to make the comparison more realistic (90). Thus, the formation constant for the Cu2OH+ complex above applies for the standard reference state of 1 M Cu2 +. In contrast, in 10 6 M Cu2+, for example, the pH at which Cu2(OH) + would form is raised from pH 5.6 to 11.6, ignoring the fact that Cu(OH)2(s) would precipitate out long before this pH as reached. By comparison, the acidity of the Cu2(0-BISTREN) complex is not affected by dilution and would still form the hydroxide complex at pH 3.9 if present at a 10"6 M concentration. 

Hansen, P., Andersson, L., and Lindeberg, G., Purification of cysteine-containing synthetic peptides via the selective binding of the a-amino group to immobilised Cu2+ and Ni2+ ions, /. Chromatogr. A, 723, 51, 1996. 

The Fur protein from E. coli was isolated in one step due to its high affinity for metal-chelate columns loaded with zinc. In DNase footprinting experiments, the Fur protein was shown to bind DNA in the promoter region of several iron-regulated genes. The consensus sequence, called the Fur box, is GATAATGATAATCATT ATC. In vitro binding is dependent on the divalent cations Co2+ Mn2+ /s Cd2+ Cu2+ at 150 iM, while Fe2+ seemed to be less active at this concentration, probably due to oxidation to Fe3+ (De Lorenzo et al., 1987). The unspecificity for divalent metals observed in vitro shows that the cells have to select the ions transported carefully and have to balance their active concentrations. In addition, it is a caveat for the experimenter to test a hypothesis on metal-ion specificity not only in vitro, but also in vivo. 

The equivalent reaction is not observed with iron. Cu(I) catalyses the Fenton reaction with hydrogen peroxide, just as Fe(II) does. The Cu(I) state exhibits the ability to bind and activate dioxygen via Cu2(p-ri2 ri2-02) and Cu2(p-0)2 species. 

The binding energy of the metal ions with non-metal anions increases in the series to a maximum at Cu2+ (or Cu+). 

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