This review focuses on the current knowledge on the involvement of metal ions in signaling processes within the cell, in both physiological and pathological conditions. The first section is devoted to the recent discoveries on magnesium and calcium-dependent signal transduction—the most recognized signaling agents among metals. The following sections then describe signaling pathways where zinc, copper, and iron play a key role. There are many systems in which changes in intra- and extra-cellular zinc and copper concentrations have been linked to important downstream events, especially in nervous signal transduction. Iron signaling is mostly related with its homeostasis. However, it is also involved in a recently discovered type of programmed cell death, ferroptosis. The important differences in metal ion signaling, and its disease-leading alterations, are also discussed.

A series of novel ferrichrome (FC) analogs was designed based on the X-ray structure of FC in the FhuA transporter of Escherichia coli. Two strategies were employed: the first strategy optimized the overall size and relative orientation of H-bonding interactions. The second strategy increased H-bonding interactions by introducing external H-donors onto analogs’ backbone. Tris-amino templates were coupled to succinic or aspartic acid, and the second carboxyl was used for hydroxamate construction. Succinic acid provided analogs without substituents, whereas aspartic acid generated analogs with external amines (i.e. H-donors). All analogs had similar physicochemical properties, yet the biological activity in Pseudomonas putida and E. coli showed great variation. While some analogs targeted specifically P. putida, others were active in both strains thus exhibiting broad-spectrum activity (as in native FC). Narrow-spectrum or species-specificity might find application in microbial diagnostic kits, while broad-spectrum recognition may have advantages in therapeutics as siderophore–drug conjugates. The differences in the structure and range of microbial recognition helped us in formulating guidelines for minimal essential parameters required for inducing broad-spectrum activity.

Amide groups of the peptide backbone are very weak acids. In fact, their deprotonation in water solution is not a phenomenon usually observed in the measuring range of a glass electrode unless the proton is displaced by a metal such as Cu(II) or Ni(II). Other metals are not usually expected to deprotonate and bind to amide nitrogens, although, lately, some controversies have started to arise in the literature, suggesting that Zn(II) and Fe(II) may be capable of doing so. In order to clarify this phenomenon, we chose to study simple metal-peptide systems with Ala-to-Pro mutations, which excluded further amides from binding. A comparison of the metal-binding modes of Ac-AAAHAAA-NH₂, Ac-AAPHAAA-NH₂, and Ac-AAPHPAA-NH₂ complexes with Cu(II), Zn(II), and Fe(II) is a simple and elegant way of showing that neither Zn(II) nor Fe(II) is able to deprotonate and bind to amide nitrogens.

Combined potentiometric titration and isothermal titration calorimetry (ITC) methods were used to study the interactions of nickel(II) ions with the N-terminal fragments and histidine-rich fragments of Hpn-like protein from two Helicobacter pylori strains (11637 and 26695). The ITC measurements were performed at various temperatures and buffers in order to extract proton-independent reaction enthalpies of nickel binding to each of the studied protein fragments. We bring up the problem of ITC results of nickel binding to the Hpn-like protein being not always compatible with those from potentiometry and MS regarding the stoichiometry and affinity. The roles of the ATCUN motif and multiple His and Gln residues in Ni(II) binding are discussed. The results provided the possibility to compare the Ni(II) binding properties between N-terminal and histidine-rich part of Hpn-like protein and between N-terminal parts of two Hpn-like strains, which differ mainly in the number of glutamine residues.

Heat shock proteins (HSPs) are part of the cell’s molecular chaperone system responsible for the proper folding (or refolding) of proteins. They are expressed in cells of a wide variety of organisms, from bacteria and fungi to humans. While some HSPs require metal ions for proper functioning, others are expressed as a response of the organism to either essential or toxic metal ions. Their presence can influence the occurrence of cellular processes, even those as significant as programmed cell death. The development of research methods and structural modeling has enabled increasingly accurate recognition of new HSP functions, including their role in maintaining metal ion homeostasis. Current investigations on the expression of HSPs in response to heavy metal ions include not only the direct effect of these ions on the cell but also analysis of reactive oxygen species (ROS) and the increased production of HSPs with increasing ROS concentration. This minireview contains information about the direct and indirect interactions of heat shock proteins with metal ions, both those of biological importance and heavy metals.

Introduction: Copper (II) and zinc (II) ions are essential microelements in the human body, interacting with numerous biologically active molecules, including proteins and peptides. The precise identification of binding sites, complete with the detailed characterization of binding amino acid residues, is of great importance. This is particularly significant in the context of uncovering the mechanisms of diseases associated with single nucleotide polymorphisms (SNPs), and consequently, developing effective treatments.Methods: Two methodological approaches were applied to study the complexation behavior. In the first, ligand and metal ions were mixed at low pH, and complexes formed upon gradual pH increase (via NaOH addition). The formation of different complex forms at changing pH was observed, and stability constants were determined. Spectroscopic data allowed prediction of coordination modes linked to structural changes. The second approach involved complex formation in buffered solutions at fixed pH. Here, metal ion solution was added to partially deprotonated ligands, potentially influencing the complexation behavior compared to the first method.Results and Discussion: This study highlights the importance of His-131 and Glu-126 residues in Cu²⁺ and Zn²⁺ ion binding by peptide fragments of the HSPB1 protein. These residues are essential for both the stability of the complexes and the nature of their interaction with the metal ions. Analytical methods exploring complexation behavior across a pH range of 2–10 and in buffer solutions provide a comprehensive view of the thermodynamic properties of the studied systems. This enables the prediction of their behavior under diverse conditions.