The effect of a membrane-mimicking environment on the interactions of Cu2+ with an amyloidogenic fragment of chicken prion protein

Prion proteins (PrP) from different species have the ability to tightly bind Cu2+ ions

The Eighth Central European Conference "Chemistry towards Biology": snapshot

The Eighth Central European Conference "Chemistry towards Biology" was held in Brno, Czech Republic, on 28 August – 1 September 2016The Eighth Central European Conference "Chemistry towards Biology" was held in Brno, Czech Republic, on 28 August-1 September 2016 to bring together experts in biology, chemistry and design of bioactive compounds; promote the exchange of scientific results, methods and ideas; and encourage cooperation between researchers from all over the world. The topics of the conference covered "Chemistry towards Biology", meaning that the event welcomed chemists working on biology-related problems, biologists using chemical methods, and students and other researchers of the respective areas that fall within the common scope of chemistry and biology. The authors of this manuscript are plenary speakers and other participants of the symposium and members of their research teams. The following summary highlights the major points/topics of the meeting

Zinc(II)—The Overlooked Éminence Grise of Chloroquine’s Fight against COVID-19?

The authors would like to thank Agnieszka Michalczuk for providing us with her artistic vision of SARS-CoV-2.Zn(II) is an inhibitor of SARS-CoV-2′s RNA-dependent RNA polymerase, and chloroquine and hydroxychloroquine are Zn(II) ionophores–this statement gives a curious mind a lot to think about. We show results of the first clinical trials on chloroquine (CQ) and hydroxychloroquine (HCQ) in the treatment of COVID-19, as well as earlier reports on the anticoronaviral properties of these two compounds and of Zn(II) itself. Other FDA-approved Zn(II) ionophores are given a decent amount of attention and are thought of as possible COVID-19 therapeutics.National Science Center, Poland UMO-2017/26/A/ST5/00363 UMO-2017/26/A/ST5/0036

Influence of membrane environments and copper ions on the structural features of amyloidogenic proteins correlated to neurodegeneration

Amyloidogenic proteins are associated with severe neurodegenerative disorders afflicting millions of people worldwide. The main hallmarks of these diseases are the presence of amyloid plaques in the brain, primarily formed by fibrils of misfolded cellular proteins. The process leading to protein aggregation, is far from completely understood. However, it is well accepted that many factors are able to influence the morphology and kinetics of amyloids formation. In the last years, a plethora of studies have suggested that the aggregation process is greatly influenced by the interactions of these proteins with copper and membranes. Amyloidogenic proteins undergo large conformational changes in the presence of membranes and show the presence of stable α helix structures in the presence of high concentrations of unilamellar vesicles or detergent micelles. The regions involved in the helicoidal rearrangements are those which are critical for protein aggregation. In addition, the α helix structuring of amyloidogenic proteins may strongly affect copper binding, in terms of donor atoms and complex stability since metal binding domains are often located near regions experiencing transitions from random-coil to α helix conformations

Investigation of metal interactions with YrpE protein of Bacillus subtilis by a polyhistidine peptide model

The use of model peptides that can simulate the behaviour of a protein domain is a very successful analytical method to study the metal coordination sites in biological systems. Here we study zinc and copper binding ability of the sequence HTHEHSHDHSHAH, which serves as model for the metal interactions with YrpE, a putative metal-binding protein of the ZinT family identified in Bacillus subtilis. Compared to other ZinT proteins secreted by Gram-negative bacteria, the metal-coordination properties of YrpE N-terminal histidine-rich domain have not been yet characterized. Different independent analytical methods, aimed at providing information on the stability and structure of the formed species, have been employed, including potentiometric titrations, electrospray ionization mass spectrometry, UV-Vis spectrophotometry, circular dichroism and electron paramagnetic resonance spectroscopy. The obtained speciation models and equilibrium constants allowed to compare the metal-binding ability of the investigated polyhistidine sequence with that of other well-known histidine-rich peptides. Our thermodynamic results revealed that the YrpE domain HTHEHSHDHSHAH forms more stable metal complexes than other His-rich domains of similar ZinT proteins. Moreover, the studied peptide, containing the alternated (-XH-)n motif, proved to be even more effective than the His6-tag (widely used in immobilized metal ion affinity chromatography) in binding zinc ions

Novel Perspective on Alzheimer's Disease Treatment: Rosmarinic Acid Molecular Interplay with Copper(II) and Amyloid beta

Alzheimer’s disease is a severe disorder that affects millions of people worldwide. It is a very debilitating disease with no cure at the moment. The necessity of finding an effective treatment is very demanding, and the entire scientific community is putting in a lot of effort to address this issue. The major hallmark of Alzheimer’s disease is the presence of toxic aggregated species in the brain, impaired metal homeostasis, and high levels of oxidative stress. Rosmarinic acid is a well-known potent antioxidant molecule, the efficacy of which has been proved both in vitro and in vivo. In this study, we investigated the possible role played by rosmarinic acid as a mediator of the copper(II)-induced neurotoxicity. Several spectroscopic techniques and biological assays were applied to characterize the metal complexes and to evaluate the cytotoxicity and the mutagenicity of rosmarinic acid and its Cu(II) complex. Our data indicate that rosmarinic acid is able to interfere with the interaction between amyloid β and Cu(II) by forming an original ternary association

Specific Zn(II)-binding site in the C-terminus of Aspf2, a zincophore from <i>Aspergillus fumigatus</i>

Abstract Aspergillus fumigatus, one of the most widespread opportunistic human fungal pathogens, adapts to zinc limitation by secreting a 310 amino acid Aspf2 zincophore, able to specifically bind Zn(II) and deliver it to a transmembrane zinc transporter, ZrfC. In this work, we focus on the thermodynamics of Zn(II) complexes with unstructured regions of Aspf2; basing on a variety of spectrometric and potentiometric data, we show that the C-terminal part has the highest Zn(II)-binding affinity among the potential binding sites, and Ni(II) does not compete with Zn(II) binding to this region. The 14 amino acid Aspf2 C-terminus coordinates Zn(II) via two Cys thiolates and two His imidazoles and it could be considered as a promising A. fumigatus targeting molecule.</jats:p