Nickel Coordination Compounds: Classification and Analysis of Crystallographic and Structural Data

Melnı́k, Milan; Šramko, T.; Dunaj‐Jurčo, M.; Sirota, A.; Ay, Clive E. Hollow

doi:10.1515/revic.1994.14.1-4.1

Cited by 15 publications

(12 citation statements)

References 668 publications

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“…(26) The EXAFS analysis shows elongated M-L distances that support this, in particular a Ni-S distance of 2.28(3) Å (~0.1 Å longer than the low-spin distance, Table 4). Such high-spin Ni(II) centers have also been observed in Cys-to-Ser mutants of NiSOD, which are catalytically inactive.…”

Section: Discussionmentioning

confidence: 65%

Nickel Superoxide Dismutase: Structural and Functional Roles of His1 and Its H-Bonding Network

et al. 2015

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Crystal structures of nickel-dependent superoxide dismutases (NiSODs) reveal the presence of a H-bonding network formed between the N-H of the apical imidazole ligand from His1 and the Glu17 carboxylate from a neighboring subunit in the hexameric enzyme. This interaction is supported by another intra-subunit H-bond between Glu17 and Arg47. In this study, four mutant NiSOD proteins were produced to experimentally evaluate the roles of this H-bonding network, and compare the results with prior predictions from DFT calculations. H1A-NiSOD, which lacks the apical ligand entirely, was crystallographically characterized and reveals that in the absence of the Glu17-His1 H-bond, the active site is disordered. Subsequent characterization using X-ray absorption spectroscopy (XAS) shows that Ni(II) is bound in the expected N2S2 planar coordination site. Despite these structural perturbations, the H1A-NiSOD variant is an active catalyst with 4% of WT-NiSOD activity. Three other mutations were designed to preserve the apical imidazole ligand, but perturb the H-bonding network: R47A-NiSOD, lacks the intra-molecular H-bonding interaction, E17R/R47A-NiSOD, which retains the intra-molecular H-bond, but lacks the inter-molecular Glu17-His1 H-bond, and E17A/R47A-NiSOD, which lacks both H-bonding interactions. These variants were characterized by a combination of techniques including XAS characterization of the nickel site structure, kinetic studies employing pulse-radiolytic production of superoxide, and EPR and chemical probes of the redox activity. The results indicate that in addition to the roles in redox tuning suggested by the computational models, the Glu17-His1 H-bond plays an important structural role in the formation of the Ni-hook motif that is a critical feature of the active site.

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Section: Discussionmentioning

confidence: 65%

Nickel Superoxide Dismutase: Structural and Functional Roles of His1 and Its H-Bonding Network

et al. 2015

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“…Six-coordinate Ni(II) complexes are invariably high-spin, and five-coordinate complexes exhibit roughly a 50–50 distribution of high- and low-spin electronic configurations [55]. MCD data show that all of the Cys mutants contain high-spin Ni(II) centers [48].…”

Section: Discussionmentioning

confidence: 99%

“…Loss of the remaining thiolate upon conversion to a high-spin complex is consistent with nickel coordination chemistry. Few examples of high-spin Ni(II) thiolates have been characterized [55]. Examples include the tetrahedral Ni(S-Ar) 4 2− anions (Ni-S Avg = 2.28 Å) [56], five-coordinate trigonal-bipyramidal (Ni-S = 2.26–2.36 Å) [40, 57, 58], and a few six-coordinate complexes that utilize chelation thiolate ligands and feature very long Ni-S distances (Ni-S = 2.46–2.54 Å)[59] compared to those that are typical of low-spin complexes such as WT-NiSOD (< 2.2 Å) [35].…”

Section: Discussionmentioning

confidence: 99%

Nickel superoxide dismutase: structural and functional roles of Cys2 and Cys6

et al. 2010

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Nickel superoxide dismutase (NiSOD) is unique among the family of SOD enzymes in that it coordinates cysteine residues (Cys2 and Cys6) to the redox-active metal center and exhibits a hexameric quaternary structure. To assess the role of the Cys residues with respect to the activity of NiSOD, mutations of Cys2 and Cys6 to serine (C2S-, C6S-, and C2S/C6S-NiSOD) were carried out. The resulting mutants do not catalyze the disproportionation of superoxide, but retain the hexameric structure found for wild-type (WT) NiSOD and bind Ni(II) ions in a 1:1 stoichiometry. X-ray absorption spectroscopic (XAS) studies of the Cys mutants reveal that the nickel active-site structure for each mutant resembles that of C2S/C6S-NiSOD and demonstrate that mutation of either Cys2 or Cys6 inhibits coordination of the remaining Cys residue. Mutation of one or both Cys residue(s) in NiSOD induces the conversion of the low-spin Ni(II) site in the native enzyme to a high-spin Ni(II) center in the mutants. This result that indicates that coordination of both Cys residues is required to generate the native low-spin configurations and maintain catalytic activity. Analysis of the quaternary structure of the cysteine mutants by differential scanning calorimetry, mass spectrometry, and size-exclusion chromatography reveal that the cysteine ligands, particularly Cys2, are also important for stabilizing the hexameric quaternary structure of the native enzyme.

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“…Nickel forms not only mononuclear complexes, but also polynuclear complexes [246]. The inorganic polynuclear nickel species have no direct biological significance but they can help understand the complex structure of nickel bioinorganic species.…”

Section: Vanadium As An Therapeutic Agentmentioning

confidence: 99%

Metals, Toxicity and Oxidative Stress

Valko

Morris²,

Cronin

2005

CMC

4,300

2,664

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Metal-induced toxicity and carcinogenicity, with an emphasis on the generation and role of reactive oxygen and nitrogen species, is reviewed. Metal-mediated formation of free radicals causes various modifications to DNA bases, enhanced lipid peroxidation, and altered calcium and sulfhydryl homeostasis. Lipid peroxides, formed by the attack of radicals on polyunsaturated fatty acid residues of phospholipids, can further react with redox metals finally producing mutagenic and carcinogenic malondialdehyde, 4-hydroxynonenal and other exocyclic DNA adducts (etheno and/or propano adducts). Whilst iron (Fe), copper (Cu), chromium (Cr), vanadium (V) and cobalt (Co) undergo redox-cycling reactions, for a second group of metals, mercury (Hg), cadmium (Cd) and nickel (Ni), the primary route for their toxicity is depletion of glutathione and bonding to sulfhydryl groups of proteins. Arsenic (As) is thought to bind directly to critical thiols, however, other mechanisms, involving formation of hydrogen peroxide under physiological conditions, have been proposed. The unifying factor in determining toxicity and carcinogenicity for all these metals is the generation of reactive oxygen and nitrogen species. Common mechanisms involving the Fenton reaction, generation of the superoxide radical and the hydroxyl radical appear to be involved for iron, copper, chromium, vanadium and cobalt primarily associated with mitochondria, microsomes and peroxisomes. However, a recent discovery that the upper limit of "free pools" of copper is far less than a single atom per cell casts serious doubt on the in vivo role of copper in Fenton-like generation of free radicals. Nitric oxide (NO) seems to be involved in arsenite-induced DNA damage and pyrimidine excision inhibition. Various studies have confirmed that metals activate signalling pathways and the carcinogenic effect of metals has been related to activation of mainly redox-sensitive transcription factors, involving NF-kappaB, AP-1 and p53. Antioxidants (both enzymatic and non-enzymatic) provide protection against deleterious metal-mediated free radical attacks. Vitamin E and melatonin can prevent the majority of metal-mediated (iron, copper, cadmium) damage both in vitro systems and in metal-loaded animals. Toxicity studies involving chromium have shown that the protective effect of vitamin E against lipid peroxidation may be associated rather with the level of non-enzymatic antioxidants than the activity of enzymatic antioxidants. However, a very recent epidemiological study has shown that a daily intake of vitamin E of more than 400 IU increases the risk of death and should be avoided. While previous studies have proposed a deleterious pro-oxidant effect of vitamin C (ascorbate) in the presence of iron (or copper), recent results have shown that even in the presence of redox-active iron (or copper) and hydrogen peroxide, ascorbate acts as an antioxidant that prevents lipid peroxidation and does not promote protein oxidation in humans in vitro. Experimental results have also shown a link ...

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Nickel Coordination Compounds: Classification and Analysis of Crystallographic and Structural Data

Cited by 15 publications

References 668 publications

Nickel Superoxide Dismutase: Structural and Functional Roles of His1 and Its H-Bonding Network

Nickel Superoxide Dismutase: Structural and Functional Roles of His1 and Its H-Bonding Network

Nickel superoxide dismutase: structural and functional roles of Cys2 and Cys6

Metals, Toxicity and Oxidative Stress

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