The interaction between Cu(I) superoxide dismutase and hydrogen peroxide

Cabelli, Diane E.; Allen, Deena; Bielski, Benon H. J.; Holcman, Jerzy

doi:10.1016/s0021-9258(18)81754-9

Cited by 55 publications

(16 citation statements)

References 18 publications

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“…In addition, the latter has been shown to inhibit Sod1 peroxidase activity in a concentration-dependent manner , . Nitrite and formate have been reported to protect Sod1 from the inactivation resulting from hydrogen peroxide consumption under different conditions ,, . In contrast, the reported effects of bicarbonate-carbon dioxide range from marginal effects , to protection or accelerated inactivation of Sod1 .…”

Section: Resultsmentioning

confidence: 99%

“…On the other hand, formate is likely to be oxidized by the same Sod1-derived oxidant as nitrite, because they protect Sod1 from inactivation ,, and stimulate hydrogen peroxide consumption at alkaline pH (Figure ). One-electron oxidation of formate produces the carbon dioxide radical anion (CO 2 •− ) , , which is a reducing radical and cannot be monitored by DHR oxidation.…”

Section: Resultsmentioning

confidence: 99%

“…DHR oxidation in the control mixture up to 1.0 min was fit to a linear plot, and the rate obtained was substituted in the equation below (eq ) because DHR oxidation by the carbonate radical is too rapid to be the rate-limiting step of the process. v = k [ HC O 4 − ] [ SodCu ( I ) ] The concentration of SodCu(I) was assumed to be equal to the total enzyme concentration because the employed experimental conditions, 5 mM hydrogen peroxide and pH 8.4, should maintain most of the enzyme reduced at steady state , . The peroxymonocarbonate concentration at steady-state was assumed to be the one that can be attained in equilibrated solutions of the employed concentration of hydrogen peroxide (5 mM) and bicarbonate (10 mM), that is, 15 μM (eq ) .…”

Section: Methodsmentioning

confidence: 99%

“…The concentration of SodCu(I) was assumed to be equal to the total enzyme concentration because the employed experimental condi- (29,42). The peroxymonocarbonate concentration at steady-state was assumed to be the one that can be attained in equilibrated solutions of the employed concentration of hydrogen peroxide (5 mM) and bicarbonate (10 mM), that is, 15 µM (eq 12) (32).…”

Section: Kinetic Calculations and Simulationsmentioning

confidence: 99%

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Peroxymonocarbonate and Carbonate Radical Displace the Hydroxyl-like Oxidant in the Sod1 Peroxidase Activity under Physiological Conditions

Medinas

Toledo

Cerchiaro

et al. 2009

Chem. Res. Toxicol.

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Despite being one of the most important antioxidant defenses, Cu,Zn-superoxide dismutase (Sod1) has been frequently associated with harmful effects, including neurotoxicity. This toxicity has been attributed to immature forms of Sod1 and extraneous catalytic activities. Among these, the ability of Sod1 to function as a peroxidase may be particularly relevant because it is increased in bicarbonate buffer and produces the reactive carbonate radical. Despite many studies, how this radical forms remains unknown. To address this question, we systematically studied hSod1 peroxidase activity in the presence of nitrite, formate, and bicarbonate-carbon dioxide. Kinetic analyses of hydrogen peroxide consumption and of nitrite, formate, and bicarbonate-carbon dioxide oxidation showed that the Sod1-bound hydroxyl-like oxidant functions in the presence of nitrite and formate. In the presence of bicarbonate-carbon dioxide, this oxidant is replaced by peroxymonocarbonate, which is then reduced to the carbonate radical. Peroxymonocarbonate intermediacy was evidenced by (13)C NMR experiments showing line broadening of its peak in the presence of Zn,ZnSod1. In agreement, peroxymonocarbonate was docked into the hSod1 active site, where it interacted with the conserved Arg(143). Also, a reaction between peroxymonocarbonate and Cu(I)Sod1 was demonstrated by stopped-flow experiments. Kinetic simulations indicated that peroxymonocarbonate is produced during Sod1 turnover and not in bulk solution. In the presence of bicarbonate-carbon dioxide, sustained hSod1-mediated oxidations occurred with low steady-state concentrations of hydrogen peroxide (4-10 microM). Thus, carbonate radical formation through peroxymonocarbonate may be a key event in Sod1-induced toxicity.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Kinetic Calculations and Simulationsmentioning

confidence: 99%

See 2 more Smart Citations

Peroxymonocarbonate and Carbonate Radical Displace the Hydroxyl-like Oxidant in the Sod1 Peroxidase Activity under Physiological Conditions

Medinas

Toledo

Cerchiaro

et al. 2009

Chem. Res. Toxicol.

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show abstract

“…In the case of Cu(II)ZnSOD, however, anions such as azide, cyanide, and fluoride bind directly to the Cu(II) ion (10,34,35,58). It is likely, therefore, that superoxide enters into the first coordination sphere of the Cu(II) ion, forming a Cu(II)(O 2 -) complex, prior to the electron transfer that forms the products Cu(I) and O 2 (33,59).…”

Section: Influence Of the Sod Rack And Crystal Contacts On Thementioning

confidence: 99%

A Structure-Based Mechanism for Copper−Zinc Superoxide Dismutase^,

et al. 1999

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A reaction cycle is proposed for the mechanism of copper−zinc superoxide dismutase (CuZnSOD) that involves inner sphere electron transfer from superoxide to Cu(II) in one portion of the cycle and outer sphere electron transfer from Cu(I) to superoxide in the other portion of the cycle. This mechanism is based on three yeast CuZnSOD structures determined by X-ray crystallography together with many other observations. The new structures reported here are (1) wild type under 15 atm of oxygen pressure, (2) wild type in the presence of azide, and (3) the His48Cys mutant. Final R-values for the three structures are respectively 20.0%, 17.3%, and 20.9%. Comparison of these three new structures to the wild-type yeast Cu(I)ZnSOD model, which has a broken imidazolate bridge, reveals the following: (i) The protein backbones (the “SOD rack”) remain essentially unchanged. (ii) A pressure of 15 atm of oxygen causes a displacement of the copper ion 0.37 Å from its Cu(I) position in the trigonal plane formed by His46, His48, and His120. The displacement is perpendicular to this plane and toward the NE2 atom of His63 and is accompanied by elongated copper electron density in the direction of the displacement suggestive of two copper positions in the crystal. The copper geometry remains three coordinate, but the His48−Cu bond distance increases by 0.18 Å. (iii) Azide binding also causes a displacement of the copper toward His63 such that it moves 1.28 Å from the wild-type Cu(I) position, but unlike the effect of 15 atm of oxygen, there is no two-state character. The geometry becomes five-coordinate square pyramidal, and the His63 imidazolate bridge re-forms. The His48−Cu distance increases by 0.70 Å, suggesting that His48 becomes an axial ligand. (iv) The His63 imidazole ring tilts upon 15 atm of oxygen treatment and azide binding. Its NE2 atom moves toward the trigonal plane by 0.28 and 0.66 Å, respectively, in these structures. (v) The replacement of His48 by Cys, which does not bind copper, results in a five-coordinate square pyramidal, bridge-intact copper geometry with a novel chloride ligand. Combining results from these and other CuZnSOD crystal structures, we offer the outlines of a structure-based cyclic mechanism.

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Subunit asymmetry in the three‐dimensional structure of a human CuZnSOD mutant found in familial amyotrophic lateral sclerosis

et al. 1998

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The X-ray crystal structure of a human copper/zinc superoxide dismutase mutant (G37R CuZnSOD) found in some patients with the inherited form of Lou Gehrig's disease (FALS) has been determined to 1.9 angstroms resolution. The two SOD subunits have distinct environments in the crystal and are different in structure at their copper binding sites. One subunit (subunit[intact]) shows a four-coordinate ligand geometry of the copper ion, whereas the other subunit (subunit[broken]) shows a three-coordinate geometry of the copper ion. Also, subunit(intact) displays higher atomic displacement parameters for backbone atoms ((B) = 30 +/- 10 angstroms2) than subunit(broken) ((B) = 24 +/- 11 angstroms2). This structure is the first CuZnSOD to show large differences between the two subunits. Factors that may contribute to these differences are discussed and a possible link of a looser structure to FALS is suggested.

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The interaction between Cu(I) superoxide dismutase and hydrogen peroxide

Cited by 55 publications

References 18 publications

Peroxymonocarbonate and Carbonate Radical Displace the Hydroxyl-like Oxidant in the Sod1 Peroxidase Activity under Physiological Conditions

Peroxymonocarbonate and Carbonate Radical Displace the Hydroxyl-like Oxidant in the Sod1 Peroxidase Activity under Physiological Conditions

A Structure-Based Mechanism for Copper−Zinc Superoxide Dismutase^,

Subunit asymmetry in the three‐dimensional structure of a human CuZnSOD mutant found in familial amyotrophic lateral sclerosis

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The interaction between Cu(I) superoxide dismutase and hydrogen peroxide

Cited by 55 publications

References 18 publications

Peroxymonocarbonate and Carbonate Radical Displace the Hydroxyl-like Oxidant in the Sod1 Peroxidase Activity under Physiological Conditions

Peroxymonocarbonate and Carbonate Radical Displace the Hydroxyl-like Oxidant in the Sod1 Peroxidase Activity under Physiological Conditions

A Structure-Based Mechanism for Copper−Zinc Superoxide Dismutase,

Subunit asymmetry in the three‐dimensional structure of a human CuZnSOD mutant found in familial amyotrophic lateral sclerosis

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Resources

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A Structure-Based Mechanism for Copper−Zinc Superoxide Dismutase^,