High Enzyme Activity of a Binuclear Nickel Complex Formed with the Binding Loops of the NiSOD Enzyme**

Dóra Kelemen,István Fábián,Norbert Lihi,Nóra V May,Melinda Andrási,Attila Gáspár

doi:10.1002/chem.202002706

Dóra Kelemen, István Fábián + Show 4 more

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https://doi.org/10.1002/chem.202002706

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Abstract

Detailed equilibrium, spectroscopic and superoxide dismutase (SOD) activity studies are reported on a nickel complex formed with a new metallopeptide bearing two nickel binding loops of NiSOD. The metallopeptide exhibits unique nickel binding ability and the binuclear complex is a major species with 2×(NH2,Namide,S−,S−) donor set even in an equimolar solution of the metal ion and the ligand. Nickel(III) species were generated by oxidizing the NiII complexes with KO2 and the coordination modes were identified by EPR spectroscopy. The binuclear complex formed with the binding motifs exhibits superior SOD activity, in this respect it is an excellent model of the native NiSOD enzyme. A detailed kinetic model is postulated that incorporates spontaneous decomposition of the superoxide ion, the dismutation cycle and fast redox degradation of the binuclear complex. The latter process leads to the elimination of the SOD activity. A unique feature of this system is that the NiIII form of the catalyst rapidly accumulates in the dismutation cycle and simultaneously the NiII form becomes a minor species.

Highlights

The superoxide anion radical (O2À) is an unavoidable, highly reactive intermediate in the biochemistry of aerobic organisms
The decomposition reaction of the superoxide anion radical yields O2 and H2O2; the latter is degraded to harmless products through various pathways.[4,5]
The fitting of the titration curve confirms that 13 acid dissociation constants can be estimated, which is consistent with the expected number of acid-base processes

Summary

Introduction

Enzyme is built in homohexameric form consisting four helixbundle subunits.[7] Each monomer contains the catalytically active nickel ion, and the dismutation reaction occurs through a proton-coupled electron-transfer mechanism accompanied with the cycling of the oxidation state of nickel between + 2 and + 3.[8,9] Nickel is coordinated in the N-terminal part of the peptide This coordination motif features a loop within the first six amino acid residues (HCDLPC). Earlier studies have demonstrated that this sequence is the minimal peptide motif for mimicking the catalytic cycle as well as the binding mode of NiSOD.[10] In the case of reduced form, nickel(II) is accommodated by the binding of the terminal amino group, the peptide nitrogen and the two thiolates of cysteine residues Anchoring two binding motifs of the NiSOD enzyme by lysine

Results and Discussion

Conclusions

Conflict of interest