Special Issue "Metal Binding Proteins"
A special issue of Biomolecules (ISSN 2218-273X).
Deadline for manuscript submissions: closed (31 January 2014)
Prof. Dr. Eugene Permyakov
Director of the Institute for Biological Instrumentation of the Russian Academy of Sciences, 7 Institutskaya str., Pushchino, Moscow region 142290, Russia
Phone: +7 916 180 78 83; +7 495 624 57 49
Fax: +7 4967 33 05 22
Interests: metal binding proteins; calcium binding proteins; intrinsically disordered proteins; intrinsic protein fluorescence; parvalbumin; α-lactalbumin; S100 proteins; recoverin
Metal ions play very important role in functioning of all, without any exceptions, biological systems. From ten to twelve metals are very important for vital activity of living organisms: sodium, potassium, magnesium, calcium, manganese, iron, cobalt, zinc, nickel, vanadium, molybdenum and tungsten. Sometimes these metals are called “life metals”. Specific interactions of metal ions with proteins play very important role. Metal ions play several major roles in proteins: structural, regulatory, and enzymatic. The binding of some metal ions increase stability of proteins or protein domains. Some metal ions can regulate various cell processes being first, second or third messengers. Calcium is the most universal carrier of signals to cells. Calcium regulates all important aspects of cell activity, beginning with fertilization and ending with the apoptotic suicide at the end of the life cycle. Metal ions are an integral part of many enzymes and are indispensable in many catalytic reactions. In spite of the fact that many metal binding proteins are well studied, detailed study of structural, physico-chemical and functional properties of metal binding proteins and their interactions is still an important and actual task of modern metalloproteomics.
We cordially welcome you to join us in this endeavor. Comprehensive reviews or original research articles is most welcome. We look forward to reading your contributions.
Prof. Dr. Eugene Permyakov
Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. Papers will be published continuously (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.
Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are refereed through a peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Biomolecules is an international peer-reviewed Open Access quarterly journal published by MDPI.
Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 300 CHF (Swiss Francs). English correction and/or formatting fees of 250 CHF (Swiss Francs) will be charged in certain cases for those articles accepted for publication that require extensive additional formatting and/or English corrections.
- metal binding proteins
Biomolecules 2014, 4(1), 101-116; doi:10.3390/biom4010101
Received: 7 December 2013; in revised form: 4 January 2014 / Accepted: 7 January 2014 / Published: 10 January 2014| Cited by 1 | PDF Full-text (523 KB) | HTML Full-text | XML Full-text
Biomolecules 2014, 4(2), 390-401; doi:10.3390/biom4020390
Received: 4 February 2014; in revised form: 12 March 2014 / Accepted: 14 March 2014 / Published: 11 April 2014| PDF Full-text (379 KB) | HTML Full-text | XML Full-text
Biomolecules 2014, 4(2), 402-418; doi:10.3390/biom4020402
Received: 6 February 2014; in revised form: 21 March 2014 / Accepted: 26 March 2014 / Published: 17 April 2014| Cited by 1 | PDF Full-text (236 KB) | HTML Full-text | XML Full-text
Biomolecules 2014, 4(2), 419-434; doi:10.3390/biom4020419
Received: 6 February 2014; in revised form: 19 March 2014 / Accepted: 20 March 2014 / Published: 17 April 2014| PDF Full-text (2804 KB) | HTML Full-text | XML Full-text
Review: Metallothioneins, Unconventional Proteins from Unconventional Animals: A Long Journey from Nematodes to Mammals
Biomolecules 2014, 4(2), 435-457; doi:10.3390/biom4020435
Received: 30 January 2014; in revised form: 19 March 2014 / Accepted: 21 March 2014 / Published: 22 April 2014| PDF Full-text (1243 KB) | HTML Full-text | XML Full-text
Review: The Role of Histidine-Proline-Rich Glycoprotein as Zinc Chaperone for Skeletal Muscle AMP Deaminase
Biomolecules 2014, 4(2), 474-497; doi:10.3390/biom4020474
Received: 6 February 2014; in revised form: 8 April 2014 / Accepted: 10 April 2014 / Published: 5 May 2014| PDF Full-text (1057 KB) | HTML Full-text | XML Full-text
Biomolecules 2014, 4(2), 527-545; doi:10.3390/biom4020527
Received: 6 February 2014; in revised form: 18 April 2014 / Accepted: 18 April 2014 / Published: 16 May 2014| PDF Full-text (2377 KB) | HTML Full-text | XML Full-text
Review: Evolutionary Implications of Metal Binding Features in Different Species’ Prion Protein: An Inorganic Point of View
Biomolecules 2014, 4(2), 546-565; doi:10.3390/biom4020546
Received: 20 February 2014; in revised form: 29 April 2014 / Accepted: 6 May 2014 / Published: 23 May 2014| PDF Full-text (436 KB) | HTML Full-text | XML Full-text
Review: Structures and Metal-Binding Properties of Helicobacter pylori Neutrophil-Activating Protein with a Di-Nuclear Ferroxidase Center
Biomolecules 2014, 4(3), 600-615; doi:10.3390/biom4030600
Received: 11 January 2014; in revised form: 3 June 2014 / Accepted: 4 June 2014 / Published: 26 June 2014| PDF Full-text (2503 KB) | HTML Full-text | XML Full-text
Biomolecules 2014, 4(3), 616-645; doi:10.3390/biom4030616
Received: 18 March 2014; in revised form: 5 June 2014 / Accepted: 6 June 2014 / Published: 8 July 2014| Cited by 1 | PDF Full-text (1502 KB) | HTML Full-text | XML Full-text
Review: New Perspectives on Oxidized Genome Damage and Repair Inhibition by Pro-Oxidant Metals in Neurological Diseases
Biomolecules 2014, 4(3), 678-703; doi:10.3390/biom4030678
Received: 29 April 2014; in revised form: 24 June 2014 / Accepted: 25 June 2014 / Published: 17 July 2014| PDF Full-text (691 KB) | HTML Full-text | XML Full-text
Biomolecules 2014, 4(3), 795-811; doi:10.3390/biom4030795
Received: 26 March 2014; in revised form: 25 June 2014 / Accepted: 14 July 2014 / Published: 14 August 2014| PDF Full-text (18550 KB) | HTML Full-text | XML Full-text
The below list represents only planned manuscripts. Some of these manuscripts have not been received by the Editorial Office yet. Papers submitted to MDPI journals are subject to peer-review.
Type of Paper: Review
Title: Structure and Function of the LmbE-like Superfamily
Author: Marcy Hernick
Affiliation: Department of Pharmaceutical Sciences, Appalachian College of Pharmacy, Oakwood, VA 24631, USA; E-Mail: MHernick@acp.edu (M.H.);
Abstract: The LmbE-like superfamily is comprised of a series of enzymes that use a single catalytic metal ion to catalyze the hydrolysis various substrates. These substrates are often key metabolites for eukaryotes and prokaryotes, which makes the LmbE-like enzymes important targets for drug development. Herein we review the structure and function of the LmbE-like proteins identified to date. While this is the newest superfamily of metallohydrolases, a growing number of functionally interesting proteins from this superfamily have been characterized. Available crystal structures of LmbE-like proteins reveal a Rossman fold similar to lactate dehydrogenase, which represented a novel fold for (zinc) metallohydrolases at the time the initial structure was solved. There is remarkable structural diversity amongst the substrates for the LmbE-like enzymes that translates into functional diversity for this enzyme superfamily. The majority of enzymes identified to date are metal-dependent deacetylases that catalyze the hydrolysis of a N-acetylglucosamine moiety on substrate using a combination of amino acid side chains and a single bound metal ion, most commonly zinc or iron. Additionally, studies indicate that protein dynamics play important roles in regulating access to the active site and facilitating catalysis for at least two members of this protein superfamily.
Type of Paper: Review
Title: Effect of metals on kinetic pathway of amyloid-β aggregation
Authors: Francis Hane1 and Zoya Leonenko1,2*
1Department of Biology
2Department of Physics and Astronomy, University of Waterloo, Waterloo, ON, Canada; E-Mail: email@example.com (Z.L.)
Abstract: Metal ions, including copper, zinc, and iron, have been implicated in the pathogenesis of Alzheimer's disease through a variety of mechanisms including increased amyloid-beta affinity and redox effects. Recent reports have demonstrated that the amyloid-beta monomer does not necessarily travel through a definitive intermediate enroute to a stable amyloid fibril structure. Rather, the amyloid-beta misfolding may follow a variety of pathways resulting in a fibrillar end product or a variety of oligomeric end-products with a diversity of structures and sizes. The presence of metal ions has been demonstrated to alter the kinetic pathway of the amyloid-beta peptide which may lead to more toxic oligomeric end-products. In this work, we review the contemporary literature supporting the hypothesis that metal ions alter the reaction pathway of amyloid-beta misfolding leading to more neurotoxic species.
Type of Paper: Review
Title: Structures and metal-binding properties of Helicobacter pylori neutrophil-activating protein with a di-nuclear ferroxidase center
Author: Hideshi Yokoyama * and Satoshi Fujii
Affiliation: School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka, 422-8526, Japan; E-Mails: firstname.lastname@example.org (H.Y.); email@example.com (S.F.)
Abstract: Helicobacter pylori causes severe diseases such as chronic gastritis, peptic ulcers, and stomach cancers. H. pylori neutrophil-activating protein (HP-NAP) is an iron storage protein forming a dodecameric shell, promotes adhesion of neutrophils to endothelial cells, and induces the production of reactive oxygen radicals. HP-NAP belongs to DNA-protecting proteins under starved conditions (Dps) family, which has significant structural similarity to the ferritin family. The crystal structures of HP-NAP in an apo form and in a metal-ion bound form such as iron, zinc, and cadmium have been determined. This review focuses on the structures and metal-binding properties of HP-NAP. These metal ions bind at the di-nuclear ferroxidase center (FOC) by different coordinating patterns. In comparison with the apo structure, metal loading causes a series of conformational changes of conserved residues among HP-NAP and Dps proteins (Trp26, Asp52, and Glu56) at the FOC. HP-NAP forms as a spherical dodecamer with 23 symmetry including two kinds of pores. Metal ions are found around one of the pores, and therefore the negatively-charged pore is suitable for metal ions to pass through.
Keywords: Helicobacter pylori; neutrophil-activating protein; ferroxidase center; iron; zinc; cadmium; Dps; ferritin; solvent channel; pore
Type of Paper: Review
Title: Enhanced adsorption and recovery of uranyl ions by NikR mutant-displaying yeast
Authors: Kouichi Kuroda, Kazuki Ebisutani, Katsuya Iida, Takashi Nishitani and Mitsuyoshi Ueda
Affiliation: Division of Applied Life Sciences, Graduate School of Agriculture, Kyoto University, Kitashirakawa-Oiwake-cho, Sakyo-ku, Kyoto 606–8502, Japan; E-Mails: firstname.lastname@example.org (M.U.)
Abstract:Uranium is one of the most important metal resources, and 4.6 billion-ton of uranium is estimated to be in sea water. Therefore, the technology for recovery of uranyl ions (UO2+) from aqueous solutions is required for semi-permanent supply of uranium. In this study, NikR mutant (NikR’) protein with ability to adsorb uranyl ions was displayed on yeast cell surface. NikR protein is a Ni2+-dependent transcriptional repressor of the nickel ion uptake system in E. coli, and its mutant NikR’ protein could bind uranyl ions selectively in the interface of the two monomers. To perform the binding of metal ions in the interface of the two monomers, two metal-binding domains (MBD) of NikR’ were tandemly fused via linker peptides and displayed on yeast cell surface by fusion with cell wall-anchoring domain of α–agglutinin from yeast. The NikR’-displaying yeast with particular linker lengths showed the enhanced adsorption of uranyl ions in comparison to control strain. By treating cells with citrate buffer (pH 4.3), the uranyl
Type of Paper: Review
Title: Metallothionein, an unconventional protein in unconventional animals: a long journey from mollusk to mammals
Author: Gloria Isani
Affiliation: Clinical Biochemistry Department of Veterinary,Medical Sciences, University of Bologna, Via Tola di sopra, 50 40065 Ozzano Emilia, Bologna, Italy; E-Mail: email@example.com (G.I.)
Abstract: MT are ubiquitous low molecular weight cystein rich proteins characterized by high affinity for d10 electron configuration metals, including essential (Zn and Cu) and non essential (Cd and Hg) trace elements. The biological role of these ancient and well conserved elusive proteins is still under debate since its discovery in 1957; the main hypothesized functions are: 1) homeostasis of Zn and Cu, 2) detoxification of Cd, 3) Hg and free radical scavenging. In this review we will focus on MTs in those “unconventional animals” which are not traditionally studied in veterinary medicine but are of increasing interest in this field of research. These animals, living in different environment, represent an incredible source of physiological and biochemical adaptations which are yet partly unexplored. The study of metal-metallothionein interactions can result of great interest for clinicians and researchers working in veterinary medicine, food quality and endangered species conservation. In this review we give an overview on the MT structure and function in unconventional animals, from the well studied molluscan MTs to almost unknown MTs from wild birds and mammals.
Type of Paper: Review
Title: Evolutionary implications of metal binding features in the different species prion protein: an inorganic point of view
Author: Diego La Mendola 1 and Enrico Rizzarelli2,3
1 Dipartimento di Farmacia, Università di Pisa, Via Bonanno Pisano 6, 56126, Pisa, Italy
2 Dipartimento di Scienze Chimiche, Università degli Studi di Catania, Viale A. Doria 6, 95125 Catania, Italy
3 Istituto di Biostrutture e Bioimmagini, Consiglio Nazionale delle Ricerche (CNR) Catania, Viale A. Doria 6, 95125, Catania, Italy; E-Mail: firstname.lastname@example.org (D.L.M.)
Abstract: Prion disorders are a group of fatal neurodegenerative conditions of humans and mammals. The key molecular event in the pathogenesis of such diseases is the conformational conversion of prion protein, PrPC, into a misfolded form rich in β-sheet structure, PrPc, but detailed mechanistic aspects of prion protein conversion remain enigmatic and so the precise physiological function of PrPC in healthy individuals. Several evidences support the notion of its role in copper homeostasis. PrPC binds Cu2+ mainly through a domain composed by four to five repeats of eight amino acids. In addition to mammals, PrP homologues have also been identified in birds, reptiles, amphibians and fish. The globular domain of protein is retained in the different species suggesting that the protein carries out an essential common function. However, the comparison of amino acid sequences indicates that prion protein has evolved differently in each vertebrate class. The primary sequences are strongly conserved in each group but these exhibit a low similarity with that of mammals. The N-terminal domain of different prion shows tandem amino acid repeats with an increasing amount of histidine residues going from amphibians to mammals. The difference in the sequence affects the number of copper binding sites, the affinity and the coordination environment of metal ions, suggesting that the involvement of prion in metal homeostasis may be a specific characteristic of mammals’ prion protein. In this review we describe the similarities and the differences in the metal binding of different species’ prion protein as revealed by studies carried out on the entire protein and related peptide fragments.
Type of Paper: Article
Title: Structural studies of the zinc responsive repressor ZitR in the Zn2+-bound state and in complex with DNA operator
Author: Pierre Legrand 1, Christophe Velours 2, Bladine Pineau 1, Franck Wien1, Isabelle Poquet 3,4,* and Paloma Fernandez Varela 1,5,*
1 Synchrotron SOLEIL, L’Orme des Merisiers – Saint Aubin BP 48 91190 Gif-sur-Yvette, France
2 IMAGIF, Centre National de la Recherche Scientifique, Centre de recherche de Gif , Avenue de la Terrase - 91190 Gif-sur-Yvette, France
3 Institut Micalis (UMR1319) Domaine de Vilvert, Bât. 222 – 78352 Jouy-en-Josas, France
4 Present address: LPBA, Bât. Calmette, Institut Pasteur, 75015 Paris, France
5 Present address: Centre National de la Recherche Scientifique, Centre de recherche de Gif, Avenue de la Terrasse Bât. 34 - 91190 Gif-sur-Yvette, France; E-Mail: email@example.com (P.F.V.)
Abstract: Zinc is a transition metal both vital in trace amounts and toxic at high concentrations. Whereas in the wide majority of bacteria, zinc ABC-uptake systems are controlled by Zur proteins (Fur family), Streptococcaceae (lactococci and streptococci) uses ZitR-AdcR proteins of the MarR (multiple antibiotic resistance) family. Remarkably, in the extensively studied MarR family, bearing a conserved winged helix fold to mediate DNA binding, only the ZitR-AdcR subfamily has recently been implicated in the regulation of metal (zinc) transport. Structural characterisation of Lactococcus lactis ZitR protein, by crystallography and circular dichroism, allows deepening in the molecular bases of Zn2+ and DNA binding. Our study provides clues for understanding not only how lactococcal ZitR is a sensitive Zn2+ sensor to allow efficient adaptation to extracellular Zn2+ fluctuations, but also how its conserved winged helix domain mediates binding to DNA palindromic sites.
Keywords: transition metals; metal homeostasis; metalloregulation; metal sensor protein; protein-DNA interactions
Type of Paper: Article
Title: Zinc-Binding Cysteines: Diverse Functions and Structural Motifs
Author: Nicholas J. Pace and Eranthie Weerapana
Affiliation: Department of Chemistry, Boston College, Merkert Chemistry Center, Room 214, 2609 Beacon Street, Chestnut Hill, MA 02467, USA; E-Mail: firstname.lastname@example.org (E.M.)
Abstract: Cysteine residues are known to perform essential functions within proteins, including binding to various metal ions. In particular, cysteine residues can display high affinity toward zinc ions (Zn2+), and the resulting Zn2+-cysteine complexes are critical mediators of protein structure, catalysis and regulation. Recent advances in both experimental and theoretical platforms have accelerated the identification and functional characterization of Zn2+-bound cysteines. Zn2+-cysteine complexes have been observed across diverse protein classes and are known to facilitate a variety of cellular processes. Here, we highlight the structural characteristics and diverse functional roles of Zn2+-cysteine complexes in proteins and describe structural, computational and chemical proteomic technologies that have enabled the global discovery of novel Zn2+-binding cysteines.
Type of Paper: Article
Title: Field and lab based assessment of multiple chelators in adaptive Ni/ Cu hyper-tolerance of Deschampsia cespitosa (L.) Beauv.
Authors: Allison R. Hayward, Thomas C. Hutchinson and R. J. Neil Emery *
Affiliation: Department of Biology, Trent University, Peterborough, ON K9J 7B8, Canada; E-Mail: email@example.com (R.J.N.M.)
Abstract: The production of chelators is a mechanism often involved in adaptive metal hyper-tolerance. Potential chelators include amino acids, nicotianamine, and phytochelatins. The chelators that are involved in adaptive metal hyper-tolerance should be found at higher levels in the hyper-tolerant plants than in non-tolerant plants during metal exposure. Metal hyper-tolerant and non-tolerant populations of Deschampsia cespitosa were collected from the Sudbury region and exposed to either Ni or Cu in hydroponic solutions. In addition, field-collected tissue samples were analyzed. Chelators were quantified using updated extraction techniques and HPLC-tandem mass spectrometry. In hydroponic experiments, histidine was produced at high concentrations solely in the hyper-tolerant populations during metal exposure. In all populations, contrasting responses of chelators were found with exposure to the Ni and Cu; whereby nicotianamine was at high concentrations during Ni exposure and phytochelatins were high during Cu exposure. Moreover, a similar pattern of chelator production was seen in the roots of D. cespitosa plants collected from Ni/ Cu contaminated mine sites. The results strongly implicated histidine as a Ni chelator involved in adaptive hyper-tolerance. On the other hand, response patterns of nicotianamine and phytochelatin implicate roles in constitutive basal tolerance to Ni and Cu, respectively. Conclusions could only be reached after corroboration of controlled hydroponics and in situ sampling; the study of either approach in isolation would have resulted in misguided conclusions.
Type of Paper: Review
Title: QM/MM Molecular Dynamics Studies of Metal Binding Proteins
Author: Pietro Vidossich1 and Alessandra Magistrato2
1Universitat Autònoma de Barcelona, 08193 Cerdanyola del Vallés, Spain
2CNR-IOM@SISSA, via Bonomea 265, Trieste, Italy; E-Mail: firstname.lastname@example.org (A.M.)
Abstract: Mixed quantum-classical (QM/MM) simulations have strongly contributed to provide insights in understanding structural and mechanistic aspects of biological molecules, playing a particularly important role in metal binding proteins, where the electronic effects of the transition metals have to be explicitly taken into account for a detailed and correct description of the underlying biological process. In this review, after a brief description of the basic concepts of the method, we provide an overview of its capabilities using selected examples taken from our work. Specifically, we will focus on heme peroxidases, metallo-beta-lactamases, blue copper proteins and alfa-synuclein to show how the approach is capable of describing the catalytic and/or structural role played by transition metals (either Fe, Zn or Cu) and revealing how the protein frame directs and modulates the properties and reactivity of the metal.
Type of Paper: Review
Title: De novo design of catalytically amplified sensors for small molecules
Author: Ivan V. Korendovych
Affiliation: Department of Chemistry, Adjunct Professor, Department of Biology, Syracuse University, 2-050 Center for Science & Technology, Syracuse, NY 13244, USA; E-Mail: email@example.com (I.V.K.)
Abstract: Catalytically amplified sensors link an allosteric binding site, where analyte is bound, with a reactive site, which can catalytically convert substrate into colored or fluorescent product that can be easily measured. Such arrangement greatly improves sensor's detection limit as illustrated by successful application of ELISA-based approaches. The ability to engineer synthetic catalytic sites into non-enzymatic proteins expands the repertoire of analytes as well as the readout reactions. Here we review recent examples of small molecule sensors based on allosterically regulated enzymes and organometallic catalysts. In particular, the focus of this paper is on the biocompatible, switchable enzymes regulated by small molecules that could be used to track analytes both in vivo and in the environment.
Type of Paper: Review
Title: New Perspectives on Oxidized DNA Base Damage and Repair Inhibition by Redox Metals in Neurological Diseases
Author: Erika Guerrero 1,2, Pavana M. Hegde 1, Joy Mitra 1, K.S. Rao 2, Sankar Mitra 1 and Muralidhar L. Hegde 1,*
Affiliation: 1 Houston Methodist Research Institute, an affiliate of Weill Medical College of Cornell University, 6550 Fannin St, Smith 8-030, Houston, Texas 77030, USA; E-Mails: pdixit@HoustonMethodist.org (P.M.H.); firstname.lastname@example.org (J.M.); smitra2@HoustonMethodist.org (S.M.); mlhegde@HoustonMethodist.org(M.L.H.)
2 Institute for Scientific Research and Technology Services (INDICASAT), Panama, India; E-Mails: email@example.com (E.G.); firstname.lastname@example.org (K.S.R.)
Abstract: The primary cause(s) and mechanism(s) of neuronal death in most cases of neurodegenerative diseases including Alzheimer’s and Parkinson’s disease, is still unknown. But researchers have found consistent association of certain etiological factors e.g., oxidative stress, protein misfolding/aggregation, redox metal accumulation and various types of damage to genome in the affected brain region(s). While redox metal toxicity - both essential transition metals including iron/copper, and environmental/occupational exposure to heavy metals (e.g., cadmium, lead), received scores of attention in the last decade, it is still at a cross-road as a therapeutic target, due to the inherent complexity of metal homeostasis and lack of molecular understanding of their multiple targets in affected neurons. We recently showed that excess iron and copper salts not only induce genome damage in neurons but also inhibit their repair by specifically oxidizing NEIL DNA glycosylases which initiate the repair of oxidized DNA bases. Thus reversal of metal-induced DNA repair inhibition required both chelation and reduction of oxidized cysteines in NEILs. This underscores the importance of molecular understanding of complex toxic effects of metals for more effective metal-targeted therapeutic approaches. Here, we review the oxidative genome damage repair pathway as a target for redox metal toxicity in neurological diseases.
Keywords: redox transition metals; heavy metals; DNA base excision repair; metal toxicity; metal homeostasis; neurodegeneration; Alzheimer’s disease; Parkinson’s disease.
Last update: 10 January 2014