Copper binding domain

There is considerable similarity between domains 1, 3, and 5 with excellent matching of the (3-strands 168 a-carbon atoms of domain 3 and 149 atoms of domain 5 can be superimposed on domain 1 with a root mean square fit of only 1.0 A. Major deviations occur in the loops between the first and second, and the fourth and sixth strands. The similarity of the smaller mononuclear copper binding domains, 2,4, and 6, is even more pronounced with 147 atoms from domain 4 and 143 from domain 6 fitting domain 2 with a root mean square deviation of only 0.9 A in each case. However, although all 6 domains are based on a cupre-doxin-type fold, the various loop regions deteriorate the match between an even and an odd domain with a typical fit of 1.8 A for only 91 atoms when domain 2 is superposed onto domain 1. The superposition results are summarized as part of Table 2. 

The mechanism of AD pathogenesis still remains unclear. However, one mechanism, amyloid (3 (A(3) accumulation, may be due to the disturbance in metal homeostasis in AD brains [Strausak et al., 2001]. A(3 peptides are the major constituents of the amyloid core of senile plaques, which are derived from the amyloid precursor protein (APP) and are secreted into extracelluar spaces. Both APP and A(3 contain a copper-binding domain [Hesse et al., 1994 Atwood et al., 1998]. High concentrations of copper, zinc, and iron have been found within the amyloid deposits in AD brains [Lovell et al., 1998], A(3 peptides can be rapidly precipitated by copper under mildly acidic conditions and by zinc at low physiological (submicromolar) concentrations [Bush et al., 1994], An age-dependent binding between A(3 peptides with excess brain metals (copper, iron, and zinc) induces A(3 peptides to precipitate into metal-enriched plaques [Bush, 2002],... 

One of the earliest Schiff base macrocycles to exhibit a haemocyanine-like structure was the copper(II) perchlorate complex of 5.5 which binds readily to azide or hydroxide.8 The azide complex exhibits two square pyramidal copper binding domains with the basal plane occupied by one pyridyl nitrogen atom and two imine functionalities as well as a terminal azide ligand. The apices of the two pyramidal coordination polyhedra are linked by a single bridging azide anion. Continuing the biomimetic theme, manganese (II) cascade complexes of the unsymmetrical 5.6 have... 

All copper chaperones, as well as the copper-binding domains of copper ATPases characterized so far, show the typical consensus motif... 

A keyword search will provide access to coordinate sets from all species that are currently available as well as various site-directed mutants, type 1 copper proteins substituted with metals other than copper, and ruthenated blue copper protein derivatives. Table 1 provides a summary (with references) of the structures of blue copper-binding domains elucidated using X-ray crystallography and NMR spectroscopy. 

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