showing 29 related works from this author
Sometimes less is more—the impact of the number of His residues on the stability of Zn(ii)–SmtB and BigR4 α-5 domain complexes
2021
The increasing number of antibiotic-resistant pathogens has become one of the major health problems of modern times, including infections caused by Mycobacterium tuberculosis. One of the possible mammalian immune system responses to mycobacterial infection is the increase of the zinc(II) concentration in phagosomes to a toxic level. The mycobacterial SmtB protein belongs to the family of ArsR/SmtB transcription regulators. In the presence of high concentrations of metals, SmtB dissociates from DNA and activates the expression of metal efflux proteins. In this work, we focus on the α5 zinc(II) binding domains of SmtB/BigR4 proteins (the latter being the SmtB homolog from non-pathogenic M. sm…
Peptidomimetics – An infinite reservoir of metal binding motifs in metabolically stable and biologically active molecules
2020
The involvement of metal ions in interactions with therapeutic peptides is inevitable. They are one of the factors able to fine-tune the biological properties of antimicrobial peptides, a promising group of drugs with one large drawback - a problematic metabolic stability. Appropriately chosen, proteolytically stable peptidomimetics seem to be a reasonable solution of the problem, and the use of D-, β-, γ-amino acids, unnatural amino acids, azapeptides, peptoids, cyclopeptides and dehydropeptides is an infinite reservoir of metal binding motifs in metabolically stable, well-designed, biologically active molecules. Below, their specific structural features, metal-chelating abilities and anti…
The effect of a membrane-mimicking environment on the interactions of Cu2+ with an amyloidogenic fragment of chicken prion protein
2017
Prion proteins (PrP) from different species have the ability to tightly bind Cu2+ ions. Copper coordination sites are located in the disordered and flexible N-terminal region which contains several His anchoring sites. Among them, two His residues are found in the so called amyloidogenic PrP region which is believed to play a key role in the process leading to oligomer and fibril formation. Both chicken and human amyloidogenic regions have a hydrophobic C-terminal region rich in Ala and Val amino acids. Recent findings revealed that this domain undergoes random coil to α-helix structuring upon interaction with membrane models. This interaction might strongly impact metal binding abilities e…
Poly-Gly Region Regulates the Accessibility of Metal Binding Sites in Snake Venom Peptides
2022
It is supposed that the presence of poly-His regions in close proximity to poly-Gly domains in snake venoms is related to their biological activity; poly-His/poly-Gly (pHpG) peptides inhibit the activity of metalloproteinases during venom storage via the chelation metal ions, necessary for their proper functioning. This work shows that only the histidyl residues from the N-terminal VDHDHDH motif (but not from the poly-His tag) were the primary Zn(II) binding sites and that the poly-Gly domain situated in the proximity of a central proline residue may play a regulatory role in venom gland protection. The proline induces a kink of the peptide, resulting in steric hindrance, which may modulate…
Antimicrobial peptide–metal ion interactions – a potential way of activity enhancement
2018
Increasing bacterial and fungal drug resistance requires novel, effective antimicrobial treatments to be actively sought. Because of a general lack of resistance towards antimicrobial peptides (AMPs), they are being relied on as a novel class of therapeutics aiming to conquer drug-resistant bacteria and fungi. There are numerous ways in which AMPs might interact with pathogens, such as membrane disruption, production of ROS, inhibition of cell wall, nucleic acid and protein synthesis or by the withdrawal of essential metal ions. Biologically indispensable metal ions have a dual effect on the activity of antimicrobial peptides: (i) AMPs bind them, so that microbes cannot get enough metals es…
CH vs. HC—Promiscuous Metal Sponges in Antimicrobial Peptides and Metallophores
2023
Histidine and cysteine residues, with their imidazole and thiol moieties that deprotonate at approximately physiological pH values, are primary binding sites for Zn(II), Ni(II) and Fe(II) ions and are thus ubiquitous both in peptidic metallophores and in antimicrobial peptides that may use nutritional immunity as a way to limit pathogenicity during infection. We focus on metal complex solution equilibria of model sequences encompassing Cys–His and His–Cys motifs, showing that the position of histidine and cysteine residues in the sequence has a crucial impact on its coordination properties. CH and HC motifs occur as many as 411 times in the antimicrobial peptide database, while …
Uncapping the N-terminus of a ubiquitous His-tag peptide enhances its Cu2+ binding affinity
2019
Metal complexes with an N-terminally free and N-terminally acetylated polyhistidine region of Echis ocellatus venom, with an interesting His-rich motif present in numerous metal binding proteins from all kingdoms of life (DHDHDHHHHHHPGSSV-NH2 and Ac-DHDHDHHHHHHPGSSV-NH2) show the role of the free amino group in the thermodynamic enhancement of Cu2+, Ni2+ and Zn2+ binding. In the studied sequences, Cu2+ can be coordinated by different sets of imidazole rings, and a 3–10 helix is detected in close proximity of Cu2+ binding sites. The complexes are more stable than those with a typical His6-tag, despite a similar copper(II) coordination mode in both cases.
Bis(3,5-dimethyl-1H-pyrazolyl)selenide--a new bidentate bent connector for preparation of 1D and 2D co-ordination polymers.
2007
The synthesis and description of eight polymeric complexes formed by transition metals with the bifurcated ligand bis(3,5-dimethyl-1H-pyrazolyl)selenide are discussed together with X-ray crystal analysis as well as variable temperature magnetic susceptibility and characterization by Mossbauer spectroscopy. Preferable types of binding patterns of the ligand were determined, which include a variation of the bridging modes (cis- and trans-) and of the separation length, where the latter parameter together with bending of the ligand molecule were found to be dependent on the type of co-ordination geometry of the central atom and the nature of the anion. A strategy for increasing the structure d…
Pneumococcal HxxHxH triad – Copper(II) interactions – How important is the ‘x’?
2019
Abstract PhtA, a Streptococcus pneumoniae polyhistidine triad protein, which contributes to virulence by interacting with components of the immune system, by being involved in adherence of bacteria and in Zn(II) uptake, contains five copies of the HxxHxH sequence. Since this motif is also present in numerous Cu(II) binding proteins, we decided to focus on the bioinorganic chemistry of copper(II) with three of such PhtA repeats, in order to understand which of the PhtA triads binds Cu(II) with the highest affinity and explain if Cu(II) would be able to outcompete Zn(II) from its native binding site under physiological metal concentrations.
Copper(II)-Induced Restructuring of ZnuD, a Zinc(II) Transporter from Neisseria meningitidis.
2019
Cluster 2 (288HDDDNAHAHTH298) from Neisseria meningitidis ZnuD is a flexible loop that captures zinc(II) ions, acting as a "fishing net". We describe its Zn(II) and Cu(II) binding capabilities, focusing on the thermodynamics of such interactions and comparing them with the complexes of the 1MAHHHHHHL9-NH2 region. Copper(II) complexes with the studied ZnuD regions are thermodynamically more stable than the zinc(II) ones-Cu(II) complexes dominate in solution even in close to physiological ratios of the studied metal ions (a 10-fold excess of Zn(II) over Cu(II)). While the binding of native Zn(II) has no significant impact on the structure of its transporter, Cu(II) binding induces a conformat…
Impact of histidine spacing on modified polyhistidine tag – Metal ion interactions
2018
Abstract Histidine rich sequences are chosen both by nature and by molecular biologists due to their high affinity towards metal ions. In this work, we examine the affinity and binding modes of Cu 2+ , Ni 2+ and Zn 2+ towards two histidine tags, the common His 6 -tag (Ac-HHHHHH-NH 2 ) and its modified sequence, which also contains six histidines, but separated with two alanine residues (Ac-HAAHAAHAAHAAHAAHAA-NH 2 ). The spatial separation of histidines has an important impact on its coordination properties. Cu 2+ and Ni 2+ complexes with Ac-HHHHHH-NH 2 are more stable than those with Ac-HAAHAAHAAHAAHAAHAA-NH 2 ; the contrary is observed for Zn 2+ . In a narrow range of pH, Cu 2+ -Ac-HHHHHH-…
Specific Zn(II)-binding site in the C-terminus of Aspf2, a zincophore from Aspergillus fumigatus
2022
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…
How copper ions and membrane environment influence the structure of the human and chicken tandem repeats domain?
2019
Abstract Prion proteins (PrPs) from different species have the enormous ability to anchor copper ions. The N-terminal domain of human prion protein (hPrP) contains four tandem repeats of the –PHGGGWGQ– octapeptide sequence. This octarepeat domain can bind up to four Cu2+ ions. Similarly to hPrP, chicken prion protein (chPrP) is able to interact with Cu2+ through the tandem hexapeptide -HNPGYP- region (residues 53–94). In this work, we focused on the human octapeptide repeat (human Octa4, hPrP60–91) (Ac-PHGGGWGQPHGGGWGQPHGGGWGQPHGGGWGQ-NH2) and chicken hexapeptide repeat (chicken Hexa4, chPrP54–77) (Ac-HNPGYPHNPGYPHNPGYPHNPGYP-NH2) prion protein fragments. Due to the fact that PrP is a membr…
Cu2+ Coordination Properties of a 2-Pyridine Heptaamine Tripod: Characterization and Binding Mechanism
2009
The synthesis, protonation, and Cu(2+) coordination chemistry of a tripodal heptaamine ligand (L(1)) functionalized with 2-pyridine fragments at the ends of its three branches are reported. L(1) presents six relatively high protonation constants followed by much more reduced constant that as indicated by the UV-vis and NMR data, occur on the pyridine fragments. p[H]-metric, ESI/MS(+), EPR and UV-vis data show that L(1) is able to form mono-, di-, and trinuclear Cu(2+) complexes. Slippage movements and molecular reorganizations have been observed to occur as a function of p[H] in the 1:1 Cu(2+) complexes. The kinetic studies showed that the complex formation is fast and proceeds through a di…
Metal Complexes of Two Specific Regions of ZnuA, a Periplasmic Zinc(II) Transporter from Escherichia coli
2020
The crystal structure of ZnZnuA from Escherichia coli reveals two metal binding sites. (i) The primary binding site, His143, is located close the His-rich loop (residues 116-138) and plays a significant role in Zn(II) acquisition. (ii) The secondary binding site involves His224. In this work, we focus on understanding the interactions of two metal ions, Zn(II) and Cu(II), with two regions of ZnuA, which are possible anchoring sites for Zn(II): Ac-115MKSIHGDDDDHDHAEKSDEDHHHGDFNMHLW145-NH2 (primary metal binding site) and Ac-223GHFTVNPEIQPGAQRLHE240-NH2 (secondary metal binding site). The histidine-rich loop (residues 116-138) has a role in the capture of zinc(II), which is then further deliv…
Histidine tracts in human transcription factors: insight into metal ion coordination ability
2017
Consecutive histidine repeats are chosen both by nature and by molecular biologists due to their high affinity towards metal ions. Screening of the human genome showed that transcription factors are extremely rich in His tracts. In this work, we examine two of such His-rich regions from forkhead box and MAFA proteins—MB3 (contains 18 His) and MB6 (with 21 His residues), focusing on the affinity and binding modes of Cu2+ and Zn2+ towards the two His-rich regions. In the case of Zn2+ species, the availability of imidazole nitrogen donors enhances metal complex stability. Interestingly, an opposite tendency is observed for Cu2+ complexes at above physiological pH, in which amide nitrogens part…
Pneumococcal histidine triads – involved not only in Zn2+, but also Ni2+ binding?
2018
Polyhistidine triad proteins, which participate in Zn2+ uptake in Streptococcus pneumoniae, contain multiple copies of the HxxHxH (histidine triad motif) sequence. We focus on three such motifs from one of the most common and well-conserved polyhistidine triad proteins, PhtA, in order to understand their bioinorganic chemistry; particular focus is given to (i) understanding which of the PhtA triads binds Zn2+ with the highest affinity (and why) and (ii) explaining whether Ni2+ (also crucial for bacterial survival and virulence) could potentially outcompete Zn2+ at its native binding site. There is no significant difference in the stability of zinc(II) complexes with the three studied protei…
Zinc(II)—The Overlooked Éminence Grise of Chloroquine’s Fight against COVID-19?
2020
The authors would like to thank Agnieszka Michalczuk for providing us with her artistic vision of SARS-CoV-2.
Ag+ Complexes as Potential Therapeutic Agents in Medicine and Pharmacy
2019
Silver is a non-essential element with promising antimicrobial and anticancer properties. This work is a detailed summary of the newest findings on the bioinorganic chemistry of silver, with a special focus on the applications of Ag+ complexes and nanoparticles. The coordination chemistry of silver is given a reasonable amount of attention, summarizing the most common silver binding sites and giving examples of such binding motifs in biologically important proteins. Possible applications of this metal and its complexes in medicine, particularly as antibacterial and antifungal agents and in cancer therapy, are discussed in detail. The most recent data on silver nanoparticles are also summari…
Zn(II) and Ni(II) complexes with poly-histidyl peptides derived from a snake venom
2018
Abstract The snake venoms are complex mixtures containing many bioactive peptides and proteins; some of them are aimed to protect the snake glands, where the venom is stored, until the latter is inoculated in the victim. In the venom of some vipers of the genus Atheris , a set of peptides containing poly-His and poly-Gly segments was recently found. Poly-His peptides are not rare in Nature. Although their exact biological function is most often unknown, one thing is certain: they have good binding properties towards the transition metal ions. As a matter of fact, the imidazole side chain of histidine is one of the groups most frequently involved in metal complexation in the active sites of …
Triplet of cysteines – Coordinational riddle?
2020
Polythiol binding of metal ions plays crucial role in the proper functioning of cysteine-rich proteins that are responsible for metal homeostasis and defending processes against metal toxicity (including heavy metals detoxification). The coordination properties of cysteine residues involved in specific sequencional patterns in proteins (like those present in e.g. metallothioneins) are interesting not only from a chemical point of view but may also lead to a better understanding of the purpose and allocation of metal ions in various biomolecules. In this study, the interaction of Zn2+, Cd2+ and Ni2+ ions with four peptides containing cysteine triplet motif were studied by potentiometric and …
Structural analysis of copper(I) interaction with amyloid β peptide
2019
Abstract The N-terminal fragment of Aβ (β = beta) peptide is able to bind essential transition metal ions like, copper, zinc and iron. Metal binding usually occurs via the imidazole nitrogens of the three His residues which play a key role in the coordination chemistry. Among all the investigated systems, the interaction between copper and Amyloid β assume a biological relevance because of the interplay between the two copper oxidation states, Cu(II) and Cu(I), and their involvement in redox reactions. Both copper ions share the ability to bind Amyloid β. A huge number of investigations have demonstrated that Cu(II) anchors to the N-terminal amino and His6, His13/14 imidazole groups, while …
Poly-Xaa Sequences in Proteins - Biological Role and Interactions with Metal Ions: Chemical and Medical Aspects
2016
Background: The understanding of the bioinorganic and coordination chemistry of metalloproteins containing unusual poly-Xaa sequences, in which a single amino acid is repeated consecutively, is crucial for describing their metal binding-structure-function relationship, and therefore also crucial for understanding their medicinal potential. To the best of our knowledge, this is the first systematic review on metal complexes with polyXaa sequences. Methods: We performed a thorough search of high quality peer reviewed literature on poly-Xaa type of sequences in proteins, focusing on their biological importance and on their interactions with metal ions. Results: 228 papers were included in the…
The diversity and utility of arylthiazoline and aryloxazoline siderophores: challenges of total synthesis
2022
Siderophores are unique ferric ion chelators produced and secreted by some organisms like bacteria, fungi and plants under iron deficiency conditions. These molecules possess immense affinity and specificity for Fe3+ and other metal ions, which attracts great interest due to the numerous possibilities of application, including antibiotics delivery to resistant bacteria strains. Total synthesis of siderophores is a must since the compounds are present in natural sources at extremely small concentrations. These molecules are extremely diverse in terms of molecular structure and physical and chemical properties. This review is focused on achievements and developments in the total synthesis str…
Metal specificity of the Ni(II) and Zn(II) binding sites of the N-terminal and G-domain of E. coli HypB
2021
HypB is one of the chaperones required for proper nickel insertion into [NiFe]-hydrogenase. Escherichia coli HypB has two potential Ni(II) and Zn(II) binding sites—the N-terminal one and the so-called GTPase one. The metal-loaded HypB–SlyD metallochaperone complex activates nickel release from the N-terminal HypB site. In this work, we focus on the metal selectivity of the two HypB metal binding sites and show that (i) the N-terminal region binds Zn(II) and Ni(II) ions with higher affinity than the G-domain and (ii) the lower affinity G domain binds Zn(II) more effectively than Ni(II). In addition, the high affinity N-terminal domain, both in water and membrane mimicking SDS solution, has a…
Cyclic Analogs of Desferrioxamine E Siderophore for 68Ga Nuclear Imaging: Coordination Chemistry and Biological Activity in Staphylococcus aureus
2021
As multidrug-resistant bacteria are an emerging problem and threat to humanity, novel strategies for treatment and diagnostics are actively sought. We aim to utilize siderophores, iron-specific strong chelating agents produced by microbes, as gallium ion carriers for diagnosis, applying that Fe(III) can be successfully replaced by Ga(III) without losing biological properties of the investigated complex, which allows molecular imaging by positron emission tomography (PET). Here, we report synthesis, full solution chemistry, thermodynamic characterization, and the preliminary biological evaluation of biomimetic derivatives (FOX) of desferrioxamine E (FOXE) siderophore, radiolabeled with 68Ga …
New reaction of 1H-pyrazoles with selenium dioxide: one-pot synthesis of bis(1H-pyrazol-4-yl)selenides
2010
Abstract A novel reaction between 3- and 3,5-substituted pyrazoles with selenium dioxide proceeds with formation of bis(3R,5R′-1H-pyrazol-4-yl)selenides in high yield. On this basis, an efficient one-pot synthetic procedure has been developed. In the case of the unsubstituted pyrazole a selenonium compound has been obtained. The identity and structure of the isolated selenium derivatives have been confirmed by spectral methods and their molecular structures investigated by X-ray analysis.
General Aspects of Metal Ions as Signaling Agents in Health and Disease
2020
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 …
Zinc Binding Sites Conserved in Short Neuropeptides Containing a Diphenylalanine Motif
2019
A diphenylalanine motif in peptides plays a crucial role in supramolecular systems. The current work represents a novel strategy in which a diphenylalanine motif in the central domain of neuropeptides conserves the specific Zn2+ binding site and prevents "hopping" of the Zn2+ ion between alternative metal binding sites. Alternative metal binding sites may also include carboxylic atoms in the terminal domains of a peptide. Therefore, one needs to design a peptide in which the metal will not bind the carboxylic groups in the terminal domains. Herein, we propose that engineering and designing peptides with a diphenylalanine motif in the central domain may yield excellent metal chelators.