Copper(II) complex of sulfur-containing peptides. Characterization and similarity of electron spin resonance spectrum to the chromophore in blue copper proteins

Sugiura, Yukio; Hirayama, Yoshinobu; Tanaka, Hisashi; Ishizu, Kazuhiko

doi:10.1021/ja00852a043

Cited by 63 publications

(12 citation statements)

References 4 publications

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“…The SH parameters of the coordination mode are distinct from, but similar to, those of component I coordination mode of Cu 2+ /Aβ1–16 (Table 2). The above observations can be explained if Cu 2+ /Aβ1[isoAsp]–16 forms a stable 5-membered ring via the amino terminus and the carboxylate of isoAsp1 (Figure 2a), similar to the 5-membered chelate adopted by oxidised glutathione, in which the first residue of the tripeptide is isomerised glutamate [43]. We previously proposed a similar 5-membered chelate in the native peptide [16], however in this instance the oxygen coordination was via the carbonyl of Asp1 (Figure 2b).…”

Section: Resultsmentioning

confidence: 98%

Alzheimer's Aβ Peptides with Disease-Associated N-Terminal Modifications: Influence of Isomerisation, Truncation and Mutation on Cu2+ Coordination

2010

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BackgroundThe amyloid-β (Aβ) peptide is the primary component of the extracellular senile plaques characteristic of Alzheimer's disease (AD). The metals hypothesis implicates redox-active copper ions in the pathogenesis of AD and the Cu2+ coordination of various Aβ peptides has been widely studied. A number of disease-associated modifications involving the first 3 residues are known, including isomerisation, mutation, truncation and cyclisation, but are yet to be characterised in detail. In particular, Aβ in plaques contain a significant amount of truncated pyroglutamate species, which appear to correlate with disease progression.Methodology/Principal FindingsWe previously characterised three Cu2+/Aβ1–16 coordination modes in the physiological pH range that involve the first two residues. Based upon our finding that the carbonyl of Ala2 is a Cu2+ ligand, here we speculate on a hypothetical Cu2+-mediated intramolecular cleavage mechanism as a source of truncations beginning at residue 3. Using EPR spectroscopy and site-specific isotopic labelling, we have also examined four Aβ peptides with biologically relevant N-terminal modifications, Aβ1[isoAsp]–16, Aβ1–16(A2V), Aβ3–16 and Aβ3[pE]–16. The recessive A2V mutation preserved the first coordination sphere of Cu2+/Aβ, but altered the outer coordination sphere. Isomerisation of Asp1 produced a single dominant species involving a stable 5-membered Cu2+ chelate at the amino terminus. The Aβ3–16 and Aβ3[pE]–16 peptides both exhibited an equilibrium between two Cu2+ coordination modes between pH 6–9 with nominally the same first coordination sphere, but with a dramatically different pH dependence arising from differences in H-bonding interactions at the N-terminus.Conclusions/SignificanceN-terminal modifications significantly influence the Cu2+ coordination of Aβ, which may be critical for alterations in aggregation propensity, redox-activity, resistance to degradation and the generation of the Aβ3–× (× = 40/42) precursor of disease-associated Aβ3[pE]–x species.

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Section: Resultsmentioning

confidence: 98%

Alzheimer's Aβ Peptides with Disease-Associated N-Terminal Modifications: Influence of Isomerisation, Truncation and Mutation on Cu2+ Coordination

2010

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“…Charge transfer transitions We shall now present an interpretation of the intense absorption bands observed at about 13,000, 16,000, and 22,000 cm-l in blue copper proteins. Our analysis is based on the assumption that the energies of the highest occupied ligand orbitals in a CuN2N*S unit decrease according to 7rS > aS > 7rN* > 7rN, which would appear to be reasonable in view of the results obtained from studies of charge transfer spectra of related, square planar copper(II) complexes (30)(31)(32)(33)(34) (35). The rotational strength may also be determined from the experimental quantity AE, or El -E,, according to Eq.…”

Section: Resultsmentioning

confidence: 97%

Spectroscopic studies and a structural model for blue copper centers in proteins.

Solomon¹,

Hare²,

Gray³

1976

Proc. Natl. Acad. Sci. U.S.A.

161

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Distorted tetrahedral Cu(II) should exhibit d-d transitions well below 10,000 cm1, assuming that the ligand field is not unusually strong. We have undertaken, therefore, a detailed investigation of the near-infrared absorption, CD, and magnetic circular dichroism (MCD) spectra of stellacyanin, plastocyanin, and azurin. Detailed analysis of these and analogous visible spectral data has allowed assignments to be made of both the d-d and charge transfer transitions. Interpretation of the charge transfer spectra has been aided further by the identification of the probable ligands of Cu(II) in bean plastocyanin. MATERIALS AND METHODSFrench bean plastocyanin (Phaseolus vulgaris) (18), azurin (Pseudomonas aeruginosa) (19), and stellacyanin (Rhus vernicifera) (20) were purified by standard methods. Near-infrared spectra were obtained on protein films to minimize interference by water absorption and permit a wide variation of temperature. The protein solutions were dialyzed against deionized distilled water and concentrated, first by pressurized membrane ultrafiltration and then, by placing drops on a plexiglas disk in a metal dessicator over Drierite. After three of four drops had been successively concentrated (ten to fifteen for the thick films), the film was prepared'by transferring the disk to a dessicator containing a saturated potassium acetate solution. This controlled humidity allowed the film to form slowly, thereby preventing most of the cracking caused by rapid removal of excess water. The drying process was halted by transfer of the film to a dessicator charged with a saturated sodium hydrogen phosphate solution.The near-infrared CD and MCD spectra were obtained with samples run in deuterated phosphate buffer in order to extend the spectral range to about 1850 nm. Although the infrared overtones of water do not give rise to a measureable CD spectrum, an absorbance of 1.0 or greater diminished the light level to the limit of detector response. The deuterated protein solutions were prepared by evaporating unbuffered, concentrated aqueous solutions in a Drierite dessicator as described above. The films were then transferred to a

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“…The Cu 2+ ion is involved in the expression of genes for the metal-binding proteins [3] and it is also found in copper-protein combinations displaying a pseudotetrahedral symmetry and having effects in bio-systems. Through aminoxidase, copper interferes in the metabolism of the conjunctive tissue, contributing to the trophicity of vascular sides [4][5][6][7][8]. Taking into account the daily necessary quantity of Cu(II) in the organism (2-3 mg/day), its distribution and metabolism in the organism, toxicity, numerous simple or complex combinations of copper are used in the treatment of a variety of diseases, including inflammatory processes, cancer, ulcers, nervous system and heart diseases.…”

Section: Introductionmentioning

confidence: 99%

Copper(II) Complexes with Ligands Derived from 4-Amino-2,3-dimethyl-1-phenyl-3-pyrazolin-5-one: Synthesis and Biological Activity

et al. 2006

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Copper(II) complex of sulfur-containing peptides. Characterization and similarity of electron spin resonance spectrum to the chromophore in blue copper proteins

Cited by 63 publications

References 4 publications

Alzheimer's Aβ Peptides with Disease-Associated N-Terminal Modifications: Influence of Isomerisation, Truncation and Mutation on Cu2+ Coordination

Alzheimer's Aβ Peptides with Disease-Associated N-Terminal Modifications: Influence of Isomerisation, Truncation and Mutation on Cu2+ Coordination

Spectroscopic studies and a structural model for blue copper centers in proteins.

Copper(II) Complexes with Ligands Derived from 4-Amino-2,3-dimethyl-1-phenyl-3-pyrazolin-5-one: Synthesis and Biological Activity

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