A5005283064- Trace Elements in Health
- Drug Transport and Resistance Mechanisms
- Alzheimer's disease research and treatments
- Iron Metabolism and Disorders
- Amino Acid Enzymes and Metabolism
- Molecular Sensors and Ion Detection
- Hemoglobinopathies and Related Disorders
- Metal complexes synthesis and properties
- Enzyme Structure and Function
- Neuroscience and Neuropharmacology Research
- Protein Kinase Regulation and GTPase Signaling
- Tryptophan and brain disorders
- Metalloenzymes and iron-sulfur proteins
- Contact Dermatitis and Allergies
- Computational Drug Discovery Methods
- Biochemical effects in animals
- DNA and Nucleic Acid Chemistry
- Mass Spectrometry Techniques and Applications
- Erythropoietin and Anemia Treatment
- Dermatology and Skin Diseases
- Epigenetics and DNA Methylation
- Food Allergy and Anaphylaxis Research
- Heavy Metal Exposure and Toxicity
- Nanocluster Synthesis and Applications
Institute of Biochemistry and Biophysics, Polish Academy of Sciences
2016-2023
Polish Academy of Sciences
2018-2020
Aβ4-42 is a major species of Aβ peptide in the brains both healthy individuals and those affected by Alzheimer's disease. It has recently been demonstrated to bind Cu(II) with an affinity approximately 3000 times higher than commonly studied Aβ1-42 Aβ1-40 peptides, which are implicated pathogenesis Metallothionein-3, protein considered orchestrate copper zinc metabolism brain provide antioxidant protection, was shown extract from when acting its native Zn7 MT-3 form. This reaction assumed...
The superior Cu(<sc>ii</sc>) affinity of human copper transporter 1 (hCtr1) drives acquisition from serum albumin (HSA).
Silver (Ag(<sc>i</sc>)) binding to consensus zinc fingers (ZFs) causes Zn(<sc>ii</sc>) release inducing a gradual disruption of the hydrophobic core, followed by an overall conformational change and formation highly stable Ag<sub>n</sub>S<sub>n</sub>clusters.
The catabolism of β-amyloid (Aβ) is carried out by numerous endopeptidases including neprilysin, which hydrolyzes peptide bonds preceding positions 4, 10, and 12 to yield Aβ4–9 a minor Aβ12–x species. Alternative processing the amyloid precursor protein β-secretase also generates Aβ11–x All these peptides contain Xxx-Yyy-His sequence, known as an ATCUN or NTS motif, making them strong chelators Cu(II) ions. We synthesized corresponding peptides, Phe-Arg-His-Asp-Ser-Gly-OH (Aβ4–9),...
The Aβ5–x peptides (x = 38, 40, 42) are minor Aβ species in normal brains but elevated upon the application of inhibitors processing enzymes. They interesting from point view coordination chemistry for presence an Arg-His metal binding sequence at their N-terminus capable forming a 3-nitrogen (3N) three-coordinate chelate system. Similar sequences other bioactive were shown to bind Cu(II) ions biological systems. Therefore, we investigated complex formation and reactivity series truncated...
Copper transfer from Cu(<sc>ii</sc>)amyloid-β<sub>4–16</sub> to human Zn<sub>7</sub>-metallothionein-3 can be accelerated by glutamate and lowering the Zn-load of metallothionein-3 with EDTA.
The toolset of mass spectrometry (MS) is still expanding, and the number metal ion complexes researched this way growing. Cu(II) forms particularly strong peptide biological interest which are frequent objects MS studies, but quantitative aspects some reported results at odds with those experiments performed in solution. usually characterized by fast ligand exchange rates, despite their high affinity, we speculated that such kinetic lability could be responsible for observed discrepancies....
Aβ4-42 is the major subspecies of Aβ peptides characterized by avid Cu(II) binding via ATCUN/NTS motif. It thought to be produced in vivo proteolytically neprilysin, but vitro experiments presence ions indicated preferable formation C-terminally truncated species including CuIIAβ4-16, CuIIAβ4-9, and also CuIIAβ12-16, all with nearly femtomolar affinities at neutral pH. Such small complexes may serve as shuttles for copper clearance from extracellular brain spaces, on condition they could...
N-Truncated Aβ4-42 displays a high binding affinity with CuII. A mechanistic scheme of the interactions between and CuII has been proposed using fluorescence approach. The timescales different conversion steps were determined. This kinetic mechanism indicates potential synaptic functions during neurotransmission.
The Cu(II) and Zn(II) binding abilities of Gly-His-Thr-Asp-amide (GHTD-am), a tetrapeptide coreleased from the pancreas along with insulin, were studied using UV–vis circular dichroism spectroscopies, potentiometry, calorimetry. GHTD-am is very strong chelator, forming three-nitrogen complex conditional affinity constant CK at pH 7.4 4.5 × 1012 M–1. fourth coordination site can be occupied by solvent molecule or ternary ligand, such as imidazole, on order several hundred reciprocal molar....
Abstract Numerous inhibitors of protein kinases act on the basis competition, targeting ATP binding site. In this work, we present a procedure rational design bi-substrate inhibitor, complemented with biophysical assays. The type are commonly engineered by combining ligands carrying an ATP-like part peptide or peptide-mimicking fragment that determines specificity. Approach presented in paper led to generation specific system for independent screening efficient and peptides, means...
Nickel is toxic to humans. Its compounds are carcinogenic. Furthermore, nickel allergy a severe health problem that affects approximately 10-20% of The mechanism by which these conditions develop remains unclear, but it may involve the cleavage specific proteins ions. Ni(II) ions cleave peptide bond preceding Ser/Thr-Xaa-His sequence. Such sequences present in all four enzymes melatonin biosynthesis pathway, i.e., tryptophan 5-hydroxylase 1, aromatic-l-amino-acid decarboxylase, serotonin...
Abstract Aβ4‐42 is a major species of Aβ peptide in the brains both healthy individuals and those affected by Alzheimer's disease. It has recently been demonstrated to bind Cu II with an affinity approximately 3000 times higher than commonly studied Aβ1‐42 Aβ1‐40 peptides, which are implicated pathogenesis Metallothionein‐3, protein considered orchestrate copper zinc metabolism brain provide antioxidant protection, was shown extract from when acting its native Zn 7 MT‐3 form. This reaction...
Deficiency in a principal epidermal barrier protein, filaggrin (FLG), is associated with multiple allergic manifestations, including atopic dermatitis and contact allergy to nickel. Toxicity caused by dermal respiratory exposures of the general population nickel-containing objects particles deleterious side effect modern technologies. Its molecular mechanism may include peptide bond hydrolysis X
Hepcidin is an iron regulatory hormone that does not bind directly. Instead, its mature 25-peptide form (H25) contains a binding site for other metals, the so-called ATCUN/NTS (amino-terminal Cu/Ni site). The Cu(II)-hepcidin complex was previously studied, but due to poor solubility and difficult handling of peptide definitive account on equilibrium obtained reliably. In this study we performed series fluorescence competition experiments between H25 model peptides containing same determined...
Hepcidin (DTHFPICIFCCGCCHRSKCGMCCKT), an iron-regulatory hormone, is a 25-amino-acid peptide with four intramolecular disulfide bonds circulating in blood. Its hormonal activity indirect and consists of marking ferroportin-1 (an iron exporter) for degradation. biosynthesis involves the N-terminally extended precursors prepro-hepcidin pro-hepcidin, processed by peptidases to final 25-peptide form. A sequence-specific formation export oxidized bloodstream follows. In this study we considered...
Hepcidin is an iron regulatory hormone that does not bind directly. Instead, its mature 25-peptide form (H25) contains a binding site for other metals, the so-called ATCUN/NTS (amino-terminal Cu/Ni site). The Cu(II)-hepcidin complex was previously studied, but due to poor solubility and difficult handling of peptide definitive account on equilibrium obtained reliably. In this study we performed series fluorescence competition experiments between H25 model peptides containing same determined...
Hepcidin (DTHFPICIFCCGCCHRSKCGMCCKT), an iron regulatory hormone is a 25 amino acid peptide with 4 intramolecular disulfide bonds, circulating in blood. Its hormonal activity indirect and consists of marking ferroportin-1 (an exporter) for degradation. biosynthesis involves N-terminally extended precursors prepro-hepcidin pro-hepcidin, processed by peptidases to the final 25-peptide form. A sequence-specific formation bonds export oxidized bloodstream follows. In this study we considered...