0000000000388492
AUTHOR
Aleksandra Hecel
showing 15 related works from this author
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…
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.
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…
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…
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…
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…
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…
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.