Zn(II) and Ni(II) complexes with poly-histidyl peptides derived from a snake venom

Remelli, Maurizio; Brasili, Davide; Guerrini, Remo; Pontecchiani, Fabio; Potocki, Sławomir; Rowińska‐Żyrek, Magdalena; Wątły, Joanna; Kozłowski, Henryk

doi:10.1016/j.ica.2017.05.070

Cited by 12 publications

(9 citation statements)

References 45 publications

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“…The UV–vis and CD spectra recorded at pH range 3.0–8.0 ( Figure 7 A,B), do not show relevant changes, thus suggesting that the octahedral geometry is maintained. 39 …”

Section: Resultsmentioning

confidence: 99%

Coordination Properties of the Zinc Domains of BigR4 and SmtB Proteins in Nickel Systems─Designation of Key Donors

et al. 2022

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The increasing number of antibiotic-resistant pathogens has become one of the foremost health problems of modern times. One of the most lethal and multidrug-resistant bacteria is Mycobacterium tuberculosis (Mtb), which causes tuberculosis (TB). TB continues to engulf health systems due to the significant development of bacterial multidrug-resistant strains. Mammalian immune system response to mycobacterial infection includes, but is not limited to, increasing the concentration of zinc(II) and other divalent metal ions in phagosome vesicles up to toxic levels. Metal ions are necessary for the survival and virulence of bacteria but can be highly toxic to organisms if their concentrations are not strictly controlled. Therefore, understanding the mechanisms of how bacteria use metal ions to maintain their optimum concentrations and survive under lethal environmental conditions is essential. The mycobacterial SmtB protein, one of the metal-dependent transcription regulators of the ArsR/SmtB family, dissociates from DNA in the presence of high concentrations of metals, activating the expression of metal efflux proteins. In this work, we explore the properties of α5 metal-binding domains of SmtB/BigR4 proteins (the latter being the SmtB homolog from nonpathogenic Mycobacterium smegmatis ), and two mutants of BigR4 as ligands for nickel(II) ions. The study focuses on the specificity of metal–ligand interactions and describes the effect of mutations on the coordination properties of the studied systems. The results of this research reveal that the Ni(II)-BigR4 α5 species are more stable than the Ni(II)-SmtB α5 complexes. His mutations, exchanging one of the histidines for alanine, cause a decrease in the stability of Ni(II) complexes. Surprisingly, the lack of His102 resulted also in increased involvement of acidic amino acids in the coordination. The results of this study may help to understand the role of critical mycobacterial virulence factor—SmtB in metal homeostasis. Although SmtB prefers Zn(II) binding, it may also bind metal ions that prefer other coordination modes, for example, Ni(II). We characterized the properties of such complexes in order to understand the nature of mycobacterial SmtB when acting as a ligand for metal ions, given that nickel and zinc ArsR family proteins possess analogous metal-binding motifs. This may provide an introduction to the design of a new antimicrobial strategy against the pathogenic bacterium M. tuberculosis .

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“…The UV–vis and CD spectra recorded at pH range 3.0–8.0 ( Figure 7 A,B), do not show relevant changes, thus suggesting that the octahedral geometry is maintained. 39 …”

Section: Resultsmentioning

confidence: 99%

Coordination Properties of the Zinc Domains of BigR4 and SmtB Proteins in Nickel Systems─Designation of Key Donors

et al. 2022

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“…S14 ). This suggests that (1) SDS may act as a crowding agent and that (2) the α-helical structure, imposed by the solvent, ‘protects’ the amides from binding—the structure has to unwind, at least locally, in order to form a square planar complex with Cu(II) ions—a similar effect was observed in α-helical, His-rich peptides 48 – 50 .…”

Section: Resultsmentioning

confidence: 94%

Thermodynamic surprises of Cu(II)–amylin analogue complexes in membrane mimicking solutions

Dzień

Dudek

Witkowska

2022

Sci Rep

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Membrane environment often has an important effect on the structure, and therefore also on the coordination mode of biologically relevant metal ions. This is also true in the case of Cu(II) coordination to amylin analogues—rat amylin, amylin1–19, pramlintide and Ac-pramlintide, which offer N-terminal amine groups and/or histidine imidazoles as copper(II) anchoring sites. Complex stabilities are comparable, with the exception of the very stable Cu(II)–amylin1–19, which proves that the presence of the amylin C-terminus lowers its affinity for copper(II); although not directly involved, its appropriate arrangement sterically prevents early metal binding. Most interestingly, in membrane-mimicking solution, the Cu(II) affinities of amylin analogues are lower than the ones in water, probably due to the crowding effect of the membrane solution and the fact that amide coordination occurs at higher pH, which happens most likely because the α-helical structure, imposed by the membrane-mimicking solvent, prevents the amides from binding at lower pH, requiring a local unwinding of the α-helix.

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“…The last calculated complex species, ZnL, is formed at around pH 7.0 due to the deprotonation of another water molecule (pK = 8.72). This coordination model is preferred because the amide nitrogen atoms of the peptide bond do not participate in the binding of zinc ions [ 30 ]. It is consistent with the results obtained in studies on peptide ligand systems with zinc ions [ 31 ].…”

Section: Resultsmentioning

confidence: 99%

The Potential Antimicrobial Action of Human Mucin 7 15-Mer Peptide and Its Metal Complexes

Janicka-Kłos

Czapor-Irzabek

Janek

2021

IJMS

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Mucin 7 (encoded byMUC7) is a human salivary protein that has a role in the natural immune system. Fragments of mucin 7 exhibit antimicrobial activity against bacteria and yeast. Although the antimicrobial properties of peptides have been known and studied for decades, the exact mechanism of action of antimicrobial peptides (AMPs) is still unclear. It is known that some AMPs require divalent metal ions to activate their activity. Herein, we investigated three 15-mer MUC7 peptides, one of which (mother peptide, sequence, L3) is a synthetic analog of a fragment naturally excised from MUC7 (with His3, His8, and His 14) and its two structural analogs, containing only two histidine residues, His3, His13 and His8, His13 (L2 and L1, respectively). Since there is a correlation between lipophilicity, the presence of metal ions (such as Cu(II) and Zn(II)) and antimicrobial activity of AMP, antimicrobial properties of the studied peptides, as well as their complexes with Cu(II) and Zn(II) ions, were tested for activity against Gram-positive (Enterococcus faecalis, Staphylococcus epidermidis) and Gram-negative (Escherichia coli, Pseudomonas aeruginosa) bacteria and fungi (Candida albicans). The results were correlated with their lipophilicity. Coordination and thermodynamic studies (potentiometry, UV-Vis, CD) revealed the formation of mainly mononuclear complexes in solution for all studied systems with different stability in the physiological pH range.

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Zn(II) and Ni(II) complexes with poly-histidyl peptides derived from a snake venom

Cited by 12 publications

References 45 publications

Coordination Properties of the Zinc Domains of BigR4 and SmtB Proteins in Nickel Systems─Designation of Key Donors

Coordination Properties of the Zinc Domains of BigR4 and SmtB Proteins in Nickel Systems─Designation of Key Donors

Thermodynamic surprises of Cu(II)–amylin analogue complexes in membrane mimicking solutions

The Potential Antimicrobial Action of Human Mucin 7 15-Mer Peptide and Its Metal Complexes

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