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Bioinorganic Chemistry of Nickel

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A special issue of Inorganics (ISSN 2304-6740). This special issue belongs to the section "Bioinorganic Chemistry".

Deadline for manuscript submissions: closed (31 May 2019) | Viewed by 55811

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Prof. Dr. Michael J. Maroney

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Guest Editor

Department of Chemistry and Program in Molecular and Cellular Biology, University of Massachusetts Amherst, 240 Thatcher Rd. Life Sciences, Laboratory N373, Amherst, MA, USA
Interests: bioinorganic chemistry; metal trafficking; metallocenter assembly; X-ray spectroscopy; structure/function relationships in metal coordination chemistry

Prof. Dr. Stefano Ciurli

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Laboratory of Bioinorganic Chemistry, Department of Pharmacy and Biotechnology, University of Bologna, Viale G. Fanin 40, I-40127 Bologna, Italy
Interests: bioinorganic chemistry; biochemistry of metal ions; protein NMR spectroscopy; protein crystallography; nickel in biology; metal transport in biological systems; metal coordination chemistry

Special Issue Information

Dear Colleagues,

The chemistry of nickel in biological systems has been intensely investigated since the discovery of the essential role played by this transition metal in the enzyme urease, ca. 1975. Since then, several nickel-dependent enzymes have been discovered and characterized at the molecular level using structural, spectroscopic, and kinetic methods, and insight into reaction mechanisms has been elaborated using synthetic and computational models. The dual role of nickel as both an essential nutrient and as a toxin has prompted efforts to understand the molecular mechanisms of nickel toxicology and to uncover the means by which cells select nickel from among a pool of different and more readily available metal ions, and thus regulate the intracellular chemistry of nickel. This latter effort highlights the importance of proteins involved in the extra- and intra-cellular sensing of nickel, the roles of nickel-selective proteins for import and export, and nickel-responsive transcription factors, all of which are important for regulating nickel homeostasis. In this Special Issue, we wish to cover the most recent advances in all these aspects of nickel biochemistry by hosting a mix of original research articles and short critical reviews.

Prof. Dr. Michael J. Maroney
Prof. Dr. Stefano Ciurli
Guest Editors

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Keywords

nickel biochemistry
nickel homeostasis
nickel transport
nickel enzymes
nickel model chemistry

Published Papers (12 papers)

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Editorial

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2 pages, 159 KiB

Open AccessEditorial

Bioinorganic Chemistry of Nickel

by Michael J. Maroney and Stefano Ciurli

Inorganics 2019, 7(11), 131; https://0-doi-org.brum.beds.ac.uk/10.3390/inorganics7110131 - 30 Oct 2019

Cited by 5 | Viewed by 2812

Abstract

Following the discovery of the first specific and essential role of nickel in biology in 1975 (the dinuclear active site of the enzyme urease) [...] Full article

(This article belongs to the Special Issue Bioinorganic Chemistry of Nickel)

Research

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17 pages, 3200 KiB

Open AccessArticle

Preliminary Characterization of a Ni²⁺-Activated and Mycothiol-Dependent Glyoxalase I Enzyme from Streptomyces coelicolor

by Uthaiwan Suttisansanee and John F. Honek

Inorganics 2019, 7(8), 99; https://0-doi-org.brum.beds.ac.uk/10.3390/inorganics7080099 - 14 Aug 2019

Cited by 4 | Viewed by 3312

Abstract

The glyoxalase system consists of two enzymes, glyoxalase I (Glo1) and glyoxalase II (Glo2), and converts a hemithioacetal substrate formed between a cytotoxic alpha-ketoaldehyde, such as methylglyoxal (MG), and an intracellular thiol, such as glutathione, to a non-toxic alpha-hydroxy acid, such as d-lactate, and the regenerated thiol. Two classes of Glo1 have been identified. The first is a Zn²⁺-activated class and is exemplified by the Homo sapiens Glo1. The second class is a Ni²⁺-activated enzyme and is exemplified by the Escherichia coli Glo1. Glutathione is the intracellular thiol employed by Glo1 from both these sources. However, many organisms employ other intracellular thiols. These include trypanothione, bacillithiol, and mycothiol. The trypanothione-dependent Glo1 from Leishmania major has been shown to be Ni²⁺-activated. Genetic studies on Bacillus subtilis and Corynebacterium glutamicum focused on MG resistance have indicated the likely existence of Glo1 enzymes employing bacillithiol or mycothiol respectively, although no protein characterizations have been reported. The current investigation provides a preliminary characterization of an isolated mycothiol-dependent Glo1 from Streptomyces coelicolor. The enzyme has been determined to display a Ni²⁺-activation profile and indicates that Ni²⁺-activated Glo1 are indeed widespread in nature regardless of the intracellular thiol employed by an organism. Full article

(This article belongs to the Special Issue Bioinorganic Chemistry of Nickel)

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18 pages, 4478 KiB

Open AccessArticle

pH Dependent Reversible Formation of a Binuclear Ni₂ Metal-Center within a Peptide Scaffold

by Brenna C. Keegan, Daniel Ocampo and Jason Shearer

Inorganics 2019, 7(7), 90; https://0-doi-org.brum.beds.ac.uk/10.3390/inorganics7070090 - 16 Jul 2019

Cited by 3 | Viewed by 3089

Abstract

A disulfide-bridged peptide containing two Ni²⁺ binding sites based on the nickel superoxide dismutase protein, {Ni₂(SOD^mds)} has been prepared. At physiological pH (7.4), it was found that the metal sites are mononuclear with a square planar NOS₂ coordination environment with the two sulfur-based ligands derived from cysteinate residues, the nitrogen ligand derived from the amide backbone, and a water ligand. Furthermore, S K-edge X-ray absorption spectroscopy indicated that the two cysteinate sulfur atoms ligated to nickel are each protonated. Elevation of the pH to 9.6 results in the deprotonation of the cysteinate sulfur atoms, and yields a binuclear, cysteinate bridged Ni₂²⁺ center with each nickel contained in a distorted square planar geometry. At both pH = 7.4 and 9.6, the nickel sites are moderately air sensitive, yielding intractable oxidation products. However, at pH = 9.6, {Ni₂(SOD^mds)} reacts with O₂ at an ~3.5-fold faster rate than at pH = 7.4. Electronic structure calculations indicate that the reduced reactivity at pH = 7.4 is a result of a reduction in S(3p) character and deactivation of the nucleophilic frontier molecular orbitals upon cysteinate sulfur protonation. Full article

(This article belongs to the Special Issue Bioinorganic Chemistry of Nickel)

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8 pages, 1655 KiB

Open AccessCommunication

Nickel-Induced Oligomerization of the Histidine-Rich Metallochaperone CooJ from Rhodospirillum Rubrum

by Marila Alfano, Julien Pérard and Christine Cavazza

Inorganics 2019, 7(7), 84; https://0-doi-org.brum.beds.ac.uk/10.3390/inorganics7070084 - 01 Jul 2019

Cited by 5 | Viewed by 3290

Abstract

[NiFe]-carbon monoxide dehydrogenase reversibly catalyzes the oxidation of CO to CO₂. Its active site is a unique NiFe₄S₄ cluster, known as C-cluster. In Rhodospirillum rubrum, three nickel-dependent proteins, CooC, CooT and CooJ are required for Ni insertion into the active site. Among them, CooJ is a histidine-rich protein, containing two distinct and spatially separated Ni(II)-binding sites: a strictly conserved N-terminal site and a variable histidine tail at the C-terminus. Here, using biophysical techniques, we study the behavior of the protein upon Ni(II) addition. Using circular dichroism and chemical denaturation, we show that the binding of Ni(II) to the protein increases its stability. Moreover, high-order oligomers are formed through nickel–histidine tail interactions, both in vitro and in cellulo, via a dynamical and reversible process. Full article

(This article belongs to the Special Issue Bioinorganic Chemistry of Nickel)

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11 pages, 4979 KiB

Open AccessArticle

Molecular Modelling of the Ni(II)-Responsive Synechocystis PCC 6803 Transcriptional Regulator InrS in the Metal Bound Form

by Elia Barchi and Francesco Musiani

Inorganics 2019, 7(6), 76; https://0-doi-org.brum.beds.ac.uk/10.3390/inorganics7060076 - 21 Jun 2019

Cited by 6 | Viewed by 3605

Abstract

InrS (internal nickel-responsive sensor) is a transcriptional regulator found in cyanobacteria that represses the transcription of the nickel exporter NrsD in the apo form and de-represses expression of the exporter upon Ni(II) binding. Although a crystal structure of apo-InrS from Synechocystis PCC 6803 has been reported, no structure of the protein with metal ions bound is available. Here we report the results of a computational study aimed to reconstruct the metal binding site by taking advantage of recent X-ray absorption spectroscopy (XAS) data and to envisage the structural rearrangements occurring upon Ni(II) binding. The modelled Ni(II) binding site shows a square planar geometry consistent with experimental data. The structural details of the conformational changes occurring upon metal binding are also discussed in the framework of trying to rationalize the different affinity of the apo- and holo-forms of the protein for DNA. Full article

(This article belongs to the Special Issue Bioinorganic Chemistry of Nickel)

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Review

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32 pages, 7870 KiB

Open AccessReview

Nickel Metalloregulators and Chaperones

by Khadine Higgins

Inorganics 2019, 7(8), 104; https://0-doi-org.brum.beds.ac.uk/10.3390/inorganics7080104 - 19 Aug 2019

Cited by 10 | Viewed by 3641

Abstract

Nickel is essential for the survival of many pathogenic bacteria. E. coli and H. pylori require nickel for [NiFe]-hydrogenases. H. pylori also requires nickel for urease. At high concentrations nickel can be toxic to the cell, therefore, nickel concentrations are tightly regulated. Metalloregulators help to maintain nickel concentration in the cell by regulating the expression of the genes associated with nickel import and export. Nickel import into the cell, delivery of nickel to target proteins, and export of nickel from the cell is a very intricate and well-choreographed process. The delivery of nickel to [NiFe]-hydrogenase and urease is complex and involves several chaperones and accessory proteins. A combination of biochemical, crystallographic, and spectroscopic techniques has been utilized to study the structures of these proteins, as well as protein–protein interactions resulting in an expansion of our knowledge regarding how these proteins sense and bind nickel. In this review, recent advances in the field will be discussed, focusing on the metal site structures of nickel bound to metalloregulators and chaperones. Full article

(This article belongs to the Special Issue Bioinorganic Chemistry of Nickel)

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13 pages, 1843 KiB

Open AccessReview

Human Acireductone Dioxygenase (HsARD), Cancer and Human Health: Black Hat, White Hat or Gray?

by Xinyue Liu and Thomas C. Pochapsky

Inorganics 2019, 7(8), 101; https://0-doi-org.brum.beds.ac.uk/10.3390/inorganics7080101 - 18 Aug 2019

Cited by 3 | Viewed by 2914

Abstract

Multiple factors involving the methionine salvage pathway (MSP) and polyamine biosynthesis have been found to be involved in cancer cell proliferation, migration, invasion and metastasis. This review summarizes the relationships of the MSP enzyme acireductone dioxygenase (ARD), the ADI1 gene encoding ARD and other gene products (ADI1GP) with carcinomas and carcinogenesis. ARD exhibits structural and functional differences depending upon the metal bound in the active site. In the penultimate step of the MSP, the Fe²⁺ bound form of ARD catalyzes the on-pathway oxidation of acireductone leading to methionine, whereas Ni²⁺ bound ARD catalyzes an off-pathway reaction producing methylthiopropionate and carbon monoxide, a biological signaling molecule and anti-apoptotic. The relationship between ADI1GP, MSP and polyamine synthesis are discussed, along with possible role(s) of metal in modulating the cellular behavior of ADI1GP and its interactions with other cellular components. Full article

(This article belongs to the Special Issue Bioinorganic Chemistry of Nickel)

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29 pages, 7372 KiB

Open AccessReview

Theoretical Studies of Nickel-Dependent Enzymes

by Per E. M. Siegbahn, Shi-Lu Chen and Rong-Zhen Liao

Inorganics 2019, 7(8), 95; https://0-doi-org.brum.beds.ac.uk/10.3390/inorganics7080095 - 29 Jul 2019

Cited by 15 | Viewed by 4698

Abstract

The advancements of quantum chemical methods and computer power allow detailed mechanistic investigations of metalloenzymes. In particular, both quantum chemical cluster and combined QM/MM approaches have been used, which have been proven to successfully complement experimental studies. This review starts with a brief introduction of nickel-dependent enzymes and then summarizes theoretical studies on the reaction mechanisms of these enzymes, including NiFe hydrogenase, methyl-coenzyme M reductase, nickel CO dehydrogenase, acetyl CoA synthase, acireductone dioxygenase, quercetin 2,4-dioxygenase, urease, lactate racemase, and superoxide dismutase. Full article

(This article belongs to the Special Issue Bioinorganic Chemistry of Nickel)

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38 pages, 1512 KiB

Open AccessReview

Concise Review of Nickel Human Health Toxicology and Ecotoxicology

by Samuel Buxton, Emily Garman, Katherine E. Heim, Tara Lyons-Darden, Christian E. Schlekat, Michael D. Taylor and Adriana R. Oller

Inorganics 2019, 7(7), 89; https://0-doi-org.brum.beds.ac.uk/10.3390/inorganics7070089 - 12 Jul 2019

Cited by 117 | Viewed by 12415

Abstract

Nickel (Ni) metal and Ni compounds are widely used in applications like stainless steel, alloys, and batteries. Nickel is a naturally occurring element in water, soil, air, and living organisms, and is essential to microorganisms and plants. Thus, human and environmental nickel exposures are ubiquitous. Production and use of nickel and its compounds can, however, result in additional exposures to humans and the environment. Notable human health toxicity effects identified from human and/or animal studies include respiratory cancer, non-cancer toxicity effects following inhalation, dermatitis, and reproductive effects. These effects have thresholds, with indirect genotoxic and epigenetic events underlying the threshold mode of action for nickel carcinogenicity. Differences in human toxicity potencies/potentials of different nickel chemical forms are correlated with the bioavailability of the Ni²⁺ ion at target sites. Likewise, Ni²⁺ has been demonstrated to be the toxic chemical species in the environment, and models have been developed that account for the influence of abiotic factors on the bioavailability and toxicity of Ni²⁺ in different habitats. Emerging issues regarding the toxicity of nickel nanoforms and metal mixtures are briefly discussed. This review is unique in its covering of both human and environmental nickel toxicity data. Full article

(This article belongs to the Special Issue Bioinorganic Chemistry of Nickel)

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16 pages, 2889 KiB

Open AccessReview

The Maturation Pathway of Nickel Urease

by Yap Shing Nim and Kam-Bo Wong

Inorganics 2019, 7(7), 85; https://0-doi-org.brum.beds.ac.uk/10.3390/inorganics7070085 - 06 Jul 2019

Cited by 24 | Viewed by 6389

Abstract

Maturation of urease involves post-translational insertion of nickel ions to form an active site with a carbamylated lysine ligand and is assisted by urease accessory proteins UreD, UreE, UreF and UreG. Here, we review our current understandings on how these urease accessory proteins facilitate the urease maturation. The urease maturation pathway involves the transfer of Ni²⁺ from UreE → UreG → UreF/UreD → urease. To avoid the release of the toxic metal to the cytoplasm, Ni²⁺ is transferred from one urease accessory protein to another through specific protein–protein interactions. One central theme depicts the role of guanosine triphosphate (GTP) binding/hydrolysis in regulating the binding/release of nickel ions and the formation of the protein complexes. The urease and [NiFe]-hydrogenase maturation pathways cross-talk with each other as UreE receives Ni²⁺ from hydrogenase maturation factor HypA. Finally, the druggability of the urease maturation pathway is reviewed. Full article

(This article belongs to the Special Issue Bioinorganic Chemistry of Nickel)

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13 pages, 487 KiB

Open AccessReview

The Role of Non-Coding RNAs Involved in Nickel-Induced Lung Carcinogenic Mechanisms

by Yusha Zhu, Qiao Yi Chen, Alex Heng Li and Max Costa

Inorganics 2019, 7(7), 81; https://0-doi-org.brum.beds.ac.uk/10.3390/inorganics7070081 - 28 Jun 2019

Cited by 7 | Viewed by 2942

Abstract

Nickel is a naturally occurring element found in the Earth’s crust and an International Agency for Research on Cancer (IARC)-classified human carcinogen. While low levels found in the natural environment pose a minor concern, the extensive use of nickel in industrial settings such as in the production of stainless steel and various alloys complicate human exposure and health effects. Notably, interactions with nickel macromolecules, primarily through inhalation, have been demonstrated to promote lung cancer. Mechanisms of nickel-carcinogenesis range from oxidative stress, DNA damage, and hypoxia-inducible pathways to epigenetic mechanisms. Recently, non-coding RNAs have drawn increased attention in cancer mechanistic studies. Specifically, nickel has been found to disrupt expression and functions of micro-RNAs and long-non-coding RNAs, resulting in subsequent changes in target gene expression levels, some of which include key cancer genes such as p53, MDM2, c-myc, and AP-1. Non-coding RNAs are also involved in well-studied mechanisms of nickel-induced lung carcinogenesis, such as the hypoxia-inducible factor (HIF) pathway, oxidative stress, DNA damage and repair, DNA hypermethylation, and alterations in tumor suppressors and oncogenes. This review provides a summary of the currently known epigenetic mechanisms involved in nickel-induced lung carcinogenesis, with a particular focus on non-coding RNAs. Full article

(This article belongs to the Special Issue Bioinorganic Chemistry of Nickel)

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31 pages, 1413 KiB

Open AccessReview

Role of Nickel in Microbial Pathogenesis

by Robert J. Maier and Stéphane L. Benoit

Inorganics 2019, 7(7), 80; https://0-doi-org.brum.beds.ac.uk/10.3390/inorganics7070080 - 26 Jun 2019

Cited by 35 | Viewed by 5425

Abstract

Nickel is an essential cofactor for some pathogen virulence factors. Due to its low availability in hosts, pathogens must efficiently transport the metal and then balance its ready intracellular availability for enzyme maturation with metal toxicity concerns. The most notable virulence-associated components are the Ni-enzymes hydrogenase and urease. Both enzymes, along with their associated nickel transporters, storage reservoirs, and maturation enzymes have been best-studied in the gastric pathogen Helicobacter pylori, a bacterium which depends heavily on nickel. Molecular hydrogen utilization is associated with efficient host colonization by the Helicobacters, which include both gastric and liver pathogens. Translocation of a H. pylori carcinogenic toxin into host epithelial cells is powered by H₂ use. The multiple [NiFe] hydrogenases of Salmonella enterica Typhimurium are important in host colonization, while ureases play important roles in both prokaryotic (Proteus mirabilis and Staphylococcus spp.) and eukaryotic (Cryptoccoccus genus) pathogens associated with urinary tract infections. Other Ni-requiring enzymes, such as Ni-acireductone dioxygenase (ARD), Ni-superoxide dismutase (SOD), and Ni-glyoxalase I (GloI) play important metabolic or detoxifying roles in other pathogens. Nickel-requiring enzymes are likely important for virulence of at least 40 prokaryotic and nine eukaryotic pathogenic species, as described herein. The potential for pathogenic roles of many new Ni-binding components exists, based on recent experimental data and on the key roles that Ni enzymes play in a diverse array of pathogens. Full article

(This article belongs to the Special Issue Bioinorganic Chemistry of Nickel)

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