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Interaction between Metal Compounds and Proteins

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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Biochemistry".

Deadline for manuscript submissions: closed (15 June 2019) | Viewed by 19890

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Special Issue Editor

Prof. Dr. Antonello Merlino

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Guest Editor

Department of Chemical Sciences, University of Naples Federico II (Complesso Universitario di Monte Sant'Angelo), Via Cintia, 80126 Napoli, Italy
Interests: protein-metal based drug adducts; X-Ray crystallography; protein metalation; protein-ligand interactions
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear colleagues,

The binding of metal compounds to proteins plays a major role in many different fields of chemistry, from drug delivery to catalysis, from the biotechnological applications of natural and synthetic metalloenzymes to the definition of the pharmacological profiles of drugs. Here, we plan to collect original research articles, short communications, or review articles describing recent advances in the field of the characterization of the interactions between proteins and metal compounds, including metal nanoparticles.

Potential topics include, but are not limited to, the following:

Mechanistic studies of the protein metalation process

Analytical advances in the identification of protein targets for metallodrugs

Analytical advances in the determination of protein–metal recognition binding sites

Structural data on the formation of protein–metal adducts and protein–metal complexes

Identification of metal binding sites on protein structures

Biophysical studies of the interactions between proteins and metal nanoclusters/nanoparticles

Prof. Antonello Merlino
Guest Editor

Manuscript Submission Information

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. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short 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 thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

Protein–metal adducts
Protein metalation
Protein–metal nanoparticle interactions
Metal binding sites
Metallomics
Organometallic compounds
Metal-based drugs
Metalloenzymes

Related Special Issue

Interaction between Metal Compounds and Proteins 2.0 in International Journal of Molecular Sciences (2 articles)

Published Papers (6 papers)

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Research

15 pages, 5153 KiB

Open AccessArticle

Metal-Biosurfactant Complexes Characterization: Binding, Self-Assembly and Interaction with Bovine Serum Albumin

by Tomasz Janek, Lígia R. Rodrigues, Eduardo J. Gudiña and Żaneta Czyżnikowska

Int. J. Mol. Sci. 2019, 20(12), 2864; https://doi.org/10.3390/ijms20122864 - 12 Jun 2019

Cited by 18 | Viewed by 2919

Abstract

Studies on the specific and nonspecific interactions of biosurfactants with proteins are broadly relevant given the potential applications of biosurfactant/protein systems in pharmaceutics and cosmetics. The aim of this study was to evaluate the interactions of divalent counterions with the biomolecular anionic biosurfactant surfactin-C₁₅ through molecular modeling, surface tension and dynamic light scattering (DLS), with a specific focus on its effects on biotherapeutic formulations. The conformational analysis based on a semi-empirical approach revealed that Cu²⁺ ions can be coordinated by three amide nitrogens belonging to the surfactin-C₁₅ cycle and one oxygen atom of the aspartic acid from the side chain of the lipopeptide. Backbone oxygen atoms mainly involve Zn²⁺, Ca²⁺ and Mg²⁺. Subsequently, the interactions between metal-coordinated lipopeptide complexes and bovine serum albumin (BSA) were extensively investigated by fluorescence spectroscopy and molecular docking analysis. Fluorescence results showed that metal-lipopeptide complexes interact with BSA through a static quenching mechanism. Molecular docking results indicate that the metal-lipopeptide complexes are stabilized by hydrogen bonding and van der Waals forces. The biosurfactant-protein interaction properties herein described are of significance for metal-based drug discovery hypothesizing that the association of divalent metal ions with surfactin allows its interaction with bacteria, fungi and cancer cell membranes with effects that are similar to those of the cationic peptide antibiotics. Full article

(This article belongs to the Special Issue Interaction between Metal Compounds and Proteins)

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17 pages, 4358 KiB

Open AccessArticle

Studies on the Interaction between Poly-Phosphane Gold(I) Complexes and Dihydrofolate Reductase: An Interplay with Nicotinamide Adenine Dinucleotide Cofactor

by Stefania Pucciarelli, Silvia Vincenzetti, Massimo Ricciutelli, Oumarou Camille Simon, Anna Teresa Ramadori, Lorenzo Luciani and Rossana Galassi

Int. J. Mol. Sci. 2019, 20(7), 1802; https://doi.org/10.3390/ijms20071802 - 11 Apr 2019

Cited by 2 | Viewed by 3614

Abstract

A class of gold(I) phosphane complexes have been identified as inhibitors of dihydrofolate reductase (DHFR) from E. coli, an enzyme that catalyzes the reduction of dihydrofolate (DHF) to tetrahydrofolate (THF), using NADPH as a coenzyme. In this work, to comprehend the nature of the interaction at the basis of these inhibitory effects, the binding properties of bis- and tris-phosphane gold(I) chloride compounds in regards to DHFR have been studied by emission spectroscopy and spectrophotometric assays. The lack of cysteine and seleno-cysteine residues in the enzyme active site, the most favorable sites of attack of Au(I) moieties, makes this work noteworthy. The interaction with the gold compounds results into the quenching of the DHFR tryptophan’s emissions and in an enhancement of their intrinsic emission intensities. Moreover, a modulating action of NADPH is highlighted by means of an increase of the gold compound affinity toward the enzyme; in fact, the dissociation constants calculated for the interactions between DHFR and each gold compound in the presence of saturating NADPH were lower than the ones observed for the apo-enzyme. The fluorimetric data afforded to K_d values ranged from 2.22 ± 0.25 µM for (PPh₃)₂AuCl in the presence of NADPH to 21.4 ± 3.85 µM for ⁴L₃AuTf in the absence of NADPH. By elucidating the energetic aspects of the binding events, we have attempted to dissect the role played by the gold phosphane/protein interactions in the inhibitory activity, resulting in an exothermic enthalpy change and a positive entropic contribution (ΔH° = −5.04 ± 0.08 kcal/mol and ΔS° = 7.34 ± 0.005 cal/mol·K). Full article

(This article belongs to the Special Issue Interaction between Metal Compounds and Proteins)

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13 pages, 2765 KiB

Open AccessArticle

Platinum(II) O,S Complexes Inhibit the Aggregation of Amyloid Model Systems

by Daniele Florio, Anna Maria Malfitano, Sarah Di Somma, Carolin Mügge, Wolfgang Weigand, Giarita Ferraro, Ilaria Iacobucci, Maria Monti, Giancarlo Morelli, Antonello Merlino and Daniela Marasco

Int. J. Mol. Sci. 2019, 20(4), 829; https://doi.org/10.3390/ijms20040829 - 14 Feb 2019

Cited by 31 | Viewed by 3348

Abstract

Platinum(II) complexes with different cinnamic acid derivatives as ligands were investigated for their ability to inhibit the aggregation process of amyloid systems derived from Aβ, Yeast Prion Protein Sup35p and the C-terminal domain of nucleophosmin 1. Thioflavin T binding assays and circular dichroism data indicate that these compounds strongly inhibit the aggregation of investigated peptides exhibiting IC₅₀ values in the micromolar range. MS analysis confirms the formation of adducts between peptides and Pt(II) complexes that are also able to reduce amyloid cytotoxicity in human SH-SY5Y neuroblastoma cells. Overall data suggests that bidentate ligands based on β-hydroxy dithiocinnamic esters can be used to develop platinum or platinoid compounds with anti-amyloid aggregation properties. Full article

(This article belongs to the Special Issue Interaction between Metal Compounds and Proteins)

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15 pages, 2221 KiB

Open AccessArticle

Reactivity of Gold(I) Monocarbene Complexes with Protein Targets: A Theoretical Study

by Iogann Tolbatov, Cecilia Coletti, Alessandro Marrone and Nazzareno Re

Int. J. Mol. Sci. 2019, 20(4), 820; https://doi.org/10.3390/ijms20040820 - 14 Feb 2019

Cited by 32 | Viewed by 3301

Abstract

Neutral N–heterocyclic carbene gold(I) compounds such as IMeAuCl are widely used both in homogeneous catalysis and, more recently, in medicinal chemistry as promising antitumor agents. In order to shed light on their reactivity with protein side chains, we have carried out density functional theory (DFT) calculations on the thermodynamics and kinetics of their reactions with water and various nucleophiles as a model of plausible protein binding sites such as arginine, aspartic acid, asparagine, cysteine, glutamic acid, glutamine, histidine, lysine, methionine, selenocysteine, and the N-terminal group. In agreement with recent experimental data, our results suggest that IMeAuCl easily interacts with all considered biological targets before being hydrated—unless sterically prevented—and allows the establishment of an order of thermodynamic stability and of kinetic reactivity for its binding to protein residues. Full article

(This article belongs to the Special Issue Interaction between Metal Compounds and Proteins)

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14 pages, 3290 KiB

Open AccessArticle

Reaction with Proteins of a Five-Coordinate Platinum(II) Compound

by Giarita Ferraro, Tiziano Marzo, Maria Elena Cucciolito, Francesco Ruffo, Luigi Messori and Antonello Merlino

Int. J. Mol. Sci. 2019, 20(3), 520; https://doi.org/10.3390/ijms20030520 - 26 Jan 2019

Cited by 7 | Viewed by 3061

Abstract

Stable five-coordinate Pt(II) complexes have been highlighted as a promising and original platform for the development of new cytotoxic drugs. Their interaction with proteins has been scarcely studied. Here, the reactivity of the five-coordinate Pt(II) compound [Pt(I)(Me) (dmphen)(olefin)] (Me = methyl, dmphen = 2,9-dimethyl-1,10-phenanthroline, olefin = dimethylfumarate) with the model proteins hen egg white lysozyme (HEWL) and bovine pancreatic ribonuclease (RNase A) has been investigated by X-ray crystallography and electrospray ionization mass spectrometry. The X-ray structures of the adducts of RNase A and HEWL with [Pt(I)(Me)(dmphen)(olefin)] are not of very high quality, but overall data indicate that, upon reaction with RNase A, the compound coordinates the side chain of His105 upon releasing the iodide ligand, but retains the pentacoordination. On the contrary, upon reaction with HEWL, the trigonal bi-pyramidal Pt geometry is lost, the iodide and the olefin ligands are released, and the metal center coordinates the side chain of His15 probably adopting a nearly square-planar geometry. This work underlines the importance of the combined use of crystallographic and mass spectrometry techniques to characterize, in detail, the protein–metallodrug recognition process. Our findings also suggest that five-coordinate Pt(II) complexes can act either retaining their uncommon structure or functioning as prodrugs, i.e., releasing square-planar platinum complexes as bioactive species. Full article

(This article belongs to the Special Issue Interaction between Metal Compounds and Proteins)

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14 pages, 2181 KiB

Open AccessArticle

Copper Binding Features of Tropomyosin-Receptor-Kinase-A Fragment: Clue for Neurotrophic Factors and Metals Link

by Antonio Magrì and Diego La Mendola

Int. J. Mol. Sci. 2018, 19(8), 2374; https://doi.org/10.3390/ijms19082374 - 12 Aug 2018

Cited by 5 | Viewed by 2949

Abstract

The nerve growth factor (NGF) is a neurotrophin essential for the development and maintenance of neurons, whose activity is influenced by copper ions. The NGF protein exerts its action by binding to its specific receptor, TrkA. In this study, a specific domain of the TrkA receptor, region 58–64, was synthesized and its copper(II) complexes characterized by means of potentiometric and spectroscopic studies. The two vicinal histidine residues provide excellent metal anchoring sites and, at physiological pH, a complex with the involvement of the peptide backbone amide nitrogen is the predominant species. The TrkA peptide is competitive for metal binding with analogous peptides due to the N-terminal domain of NGF. These data provide cues for future exploration of the effect of metal ions on the activity of the NGF and its specific cellular receptor. Full article

(This article belongs to the Special Issue Interaction between Metal Compounds and Proteins)

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