Tomasz Fraczyk

Tomasz Fraczyk
Institute of Biochemistry and Biophysics Polish Academy of Sciences · Department of Biophysics

Ph.D.

About

56
Publications
12,385
Reads
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1,014
Citations
Citations since 2016
25 Research Items
677 Citations
2016201720182019202020212022020406080100120140
2016201720182019202020212022020406080100120140
2016201720182019202020212022020406080100120140
2016201720182019202020212022020406080100120140
Additional affiliations
April 2020 - present
Institute of Biochemistry and Biophysics Polish Academy of Sciences
Position
  • Professor (Assistant)
March 2018 - February 2020
Medical University of Warsaw
Position
  • Specialist
September 2017 - December 2020
Institute of Biochemistry and Biophysics Polish Academy of Sciences
Position
  • Auxilliary Superivisor
Description
  • Ph.D. Thesis of Karolina Bossak-Ahmad, "Ternary complex formation of His2 peptides in the presence of Cu(II) ions. A quantitative analysis of selected human and yeast peptides"
Education
July 2004 - September 2009
October 1999 - June 2004
University of Warsaw
Field of study
  • Biology

Publications

Publications (56)
Article
Full-text available
cis-Urocanic acid, a derivative of histidine, is one of the essential components of human skin. We found that it can bind nickel(ii) ions in a pH-dependent manner, with the dissociation constant in the low millimolar range, as revealed by potentiometry, and confirmed by isothermal titration calorimetry and UV-vis spectroscopy. The binding occurs wi...
Article
Full-text available
The tripeptide NH2–Gly–His–Lys–COOH (GHK), cis-urocanic acid (cis-UCA) and Cu(II) ions are physiological constituents of the human body and they co-occur (e.g., in the skin and the plasma). While GHK is known as Cu(II)-binding molecule, we found that urocanic acid also coordinates Cu(II) ions. Furthermore, both ligands create ternary Cu(II) complex...
Article
Full-text available
Link to Free Full Text: ............................................................................................................................................ https://onlinelibrary.wiley.com/share/author/J5YPUTRMDWJNMENJYC8K?target=10.1002/cbdv.202100043 ...........................................................................................
Article
Full-text available
ATCUN (amino terminal Cu(II) and Ni(II) binding) motifs chelate Cu(II) ions strongly. However, the impact of the phosphorylation of neighboring residues on such complexation has not been elucidated. The copper(II) dissociation constants of original and phosphorylated peptides from human histatin-1 and human serum albumin were compared using spectro...
Article
Full-text available
Amyloid-β (Aβ) peptides are involved in Alzheimer’s disease (AD) development. The interactions of these peptides with copper and zinc ions also seem to be crucial for this pathology. Although Cu(II) and Zn(II) ions binding by Aβ peptides has been scrupulously investigated, surprisingly, this phenomenon has not been so thoroughly elucidated for N-tr...
Article
Full-text available
Nickel is toxic to humans. Its compounds are carcinogenic. Furthermore, nickel allergy is a severe health problem that affects approximately 10–20% of humans. The mechanism by which these conditions develop remains unclear, but it may involve the cleavage of specific proteins by nickel ions. Ni(II) ions cleave the peptide bond preceding the Ser/Thr...
Article
Full-text available
Gly-His-Lys (GHK) is a tripeptide present in the human bloodstream that exhibits a number of biological functions. Its activity is attributed to the copper-complexed form, Cu(II)GHK. Little is known, however, about the molecular aspects of the mechanism of its action. Here, we examined the reaction of Cu(II)GHK with reduced glutathione (GSH), which...
Article
Human serum albumin (HSA) and the growth factor glycyl-l-histidyl-l-lysine (GHK) bind Cu2+ as part of their normal functions. GHK is found at its highest concentration in the albumin-rich fraction of plasma, leading to speculation that HSA and GHK form a ternary Cu2+ complex. Although preliminary evidence was presented 40 years ago, the structure a...
Article
Currently available chemotherapeutic treatments for blood cancers (leukemia) usually have strong side effects. More selective, efficient and less toxic anticancer agents are needed. We synthesized seven, new, optically pure (12aS)-1,3,4,12a-tetrahydropyrazino[2,1-c][1,4]benzodiazepine-6,12-(2H,11H)-dione derivatives and examined their cytotoxicity...
Article
Full-text available
The Aβ 4−42 peptide is a major beta-amyloid species in the human brain, forming toxic aggregates related to Alzheimer's Disease. It also strongly chelates Cu(II) at the N-terminal Phe-Arg-His ATCUN motif, as demonstrated in Aβ 4−16 and Aβ 4−9 model peptides. The resulting complex resists ROS generation and exchange processes and may help protect sy...
Cover Page
Full-text available
The peptide Gly–His–Lys (GHK, the natural wound healing factor) and urocanic acid (UCA, a constituent of the natural moisturizing factor) coexist in the human body, e.g., in the skin. They also share some biological activities, e.g., both modulate the immune and nervous systems. Interestingly, they have never been considered to function mutually. W...
Article
Full-text available
NiO nanoparticles and non-stoichiometric black NiO were shown to be effective sources of Ni ²⁺ ions causing sequence-selective peptide bond hydrolysis. NiO nanoparticles were as effective in this reaction as their...
Article
Full-text available
Nickel is harmful to humans, being both carcinogenic and allergenic. However, the mechanisms of this toxicity are still unresolved. We propose that Ni(II) ions disintegrate proteins by hydrolysis of peptide bonds preceding the Ser/Thr−Xaa−His sequences. Such sequences occur in nuclear localization signals (NLSs) of human phospholipid scramblase 1,...
Article
In view of previous crystallographic studies, N4-hydroxy-dCMP, a slow-binding thymidylate synthase inhibitor apparently caused "uncoupling" of the two thymidylate synthase-catalyzed reactions, including the N5,10-methylenetetrahydrofolate one-carbon group transfer and reduction, suggesting the enzyme's capacity to use tetrahydrofolate as a cofactor...
Article
The apparent affinity of human serum albumin (HSA) for divalent copper has long been the subject of great interest, due to its presumed role as the major Cu2+ -binding ligand in blood and cerebrospinal fluid. Using a combination of electronic absorption, circular dichroism and room-temperature electron paramagnetic resonance spectroscopies, togethe...
Article
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 and circular dichroism spectroscopies, potentiometry, and calorimetry. GHTD-am is a very strong Cu(II) chelator, forming a three-nitrogen complex with a conditional affinity constant ^...
Article
Sporadic Alzheimer’s disease (AD) is associated with an inefficient clearance of the β-amyloid (Aβ) peptide from the central nervous system. The protein levels and activity of the Zn2+-dependent endopeptidase neprilysin (NEP) inversely correlate with brain Aβ levels during aging and in AD. The present study considered the ability of Cu2+ ions to in...
Article
Full-text available
Crystal structures of mouse thymidylate synthase (mTS) in complexes with (1) sulfate anion, (2) 2′-deoxyuridine 5′-monophosphate (dUMP) and (3) 5-fluoro-dUMP (FdUMP) and N5,10-methylenetetrahydrofolate (meTHF) have been determined and deposited in Protein Data Bank under the accession codes 3IHI, 4E5O and 5FCT, respectively. The structures show a s...
Article
Full-text available
The intermediate filament protein keratin 8 (K8) interacts with the nucleotide-binding domain 1 (NBD1) of the cystic fibrosis transmembrane regulator (CFTR) with phenylalanine 508 deletion (ΔF508), and this interaction hampers the biogenesis of functional ΔF508-CFTR and its insertion into the plasma membrane. Interruption of this interaction may co...
Article
We describe the effect of three synthetic surfactants (anionic – sodium dodecyl sulfate (SDS), cationic – cetyltrimethylammonium bromide (CTAB) and nonionic – Triton X-100 (TX-100)) on surface properties of the type I calf skin collagen at the air/water interface in acidic solutions (pH 1.8). The protein concentration was fixed at 5 × 10⁻⁶ mol L⁻¹...
Article
Metal-assisted hydrolysis of peptide bond is a promising alternative for enzymatic cleavage of proteins with prospective applications in biochemistry and bioengineering. Many metal ions and complexes have been tested for such reactivity with a number of targets, from dipeptides through oligopeptides through proteins. The majority of reaction mechan...
Article
In the light of conflicting reports on the ability of copper(II) complexes of amyloid beta (Aβ) peptides to form ternary complexes with small molecules co-present in the biological milieu, we performed a study of coordination equilibria in the system containing Cu(II) ions, the Aβ1–16 peptide, glutamic acid and 4-(2-hydroxyethyl)-1-piperazineethane...
Article
Endogenous thymidylate synthases, isolated from tissues or cultured cells of the same specific origin, have been reported to show differing slow-binding inhibition patterns. These were reflected by biphasic or linear dependences of the inactivation rate on time and accompanied by differing inhibition parameters. Considering importance for chemother...
Article
We describe the adsorption behaviour and rheological properties of a calf skin type I collagen, and of its hydrolysates obtained using a Clostridium histolyticum collagenase (CHC) under moderate conditions (pH 7, 37°C). The effect of CHC concentration (2×10(-9)-2×10(-6)M) and incubation time (35-85min) was studied and optimised to achieve the highe...
Article
Accumulation of the β-amyloid (Aβ) peptide in extracellular senile plaques rich in copper and zinc is a defining pathological feature of Alzheimer's disease (AD). The Aβ1-x (x=16/28/40/42) peptides have been the primary focus of Cu(II) binding studies for more than 15 years; however, the N-truncated Aβ4-42 peptide is a major Aβ isoform detected in...
Article
Accumulation of the β-amyloid (Aβ) peptide in extracellular senile plaques rich in copper and zinc is a defining pathological feature of Alzheimer′s disease (AD). The Aβ1–x (x=16/28/40/42) peptides have been the primary focus of CuII binding studies for more than 15 years; however, the N-truncated Aβ4–42 peptide is a major Aβ isoform detected in bo...
Article
Full-text available
Human alpha-1 antitrypsin (AAT) is an abundant serum protein, present at a concentration of 1.0–1.5 g L−1. AAT deficiency is a genetic disease, manifesting itself with emphysema and liver cirrhosis, due to accumulation of a misfolded AAT mutant in hepatocytes. Lung AAT amount is inversely correlated with chronic obstructive pulmonary disease (COPD)...
Cover Page
Full-text available
Ni(II) ions cleave and inactivate human alpha-1 antitrypsin hydrolytically, implicating nickel exposure as a contributing factor in pathologies related to antitrypsin deficiency
Article
Poly(ADP-ribose) polymerase 1 (PARP-1) is a key eukaryotic enzyme, catalyzing the NAD+ dependent poly(ADP-ribosyl)ation of protein substrates, crucial for major DNA repair pathways, and involved in other fundamental cellular processes, such as transcription, cell cycle control, and apoptosis. Its ability to bind DNA depends on two CCHC zinc finger...
Article
Full-text available
Nickel is harmful for humans, but molecular mechanisms of its toxicity are far from being fully elucidated. One of such mechanisms may be associated with the Ni(II)-dependent peptide bond hydrolysis, which occurs before Ser/Thr in Ser/Thr-Xaa-His sequences. Human annexins A1, A2, and A8, proteins modulating the immune system, contain several such s...
Article
2-Amino-2-hydroxymethyl-propane-1,3-diol, or tris(hydroxymethyl)aminomethane (Tris), is probably the most common biochemical buffer used alone or in combination with other buffers because it is stable, unreactive, and compatible with most proteins and other biomolecules. Being nontoxic, it has even found applications in medicine. Tris is known, how...
Conference Paper
Full-text available
The binding of Ni(II) and subsequent metal-dependent hydrolysis of peptide bond occurs in sequences of peptides or proteins of the type Ser/Thr-Xaa-His. His103, His246 and His293 of human annexin A1 are located in the fragments with amino acid sequences Thr-Gly-His, Ser-Lys-His and Thr-Arg-His, respectively, which thus constitute potential nickel b...
Article
Full-text available
Crystal structures were solved of the binary complexes Trichinella spiralis and Caenorhabditis elegans thymidylate synthases with deoxyuridine monophosphate (dUMP), with crystals obtained by the vapor diffusion method in hanging drops. For the T. spiralis thymidylate synthase-dUMP complex, the diffraction data were collected at the BESSY Synchrotro...
Conference Paper
cis-Urocanic acid, a derivative of histidine, is one of the component of human skin. We found that it can bind nickel(II) ions in a pH-dependent manner, with the dissociation constant in the low millimolar range, as revealed by calorimetric measurements. The binding occurs within the physiological skin pH range, with the overall apparent pK value f...
Article
Full-text available
Highly purified preparations of thymidylate synthase, isolated from calf thymus, and L1210 parental and FdUrd-resistant cells, were found to be nitrated, as indicated by a specific reaction with anti-nitro-tyrosine antibodies, suggesting this modification to appear endogenously in normal and tumor tissues. Each human, mouse and Ceanorhabditis elega...
Article
Full-text available
Reversible phosphorylation is the most widespread posttranslational protein modification, playing regulatory role in almost every aspect of cell life. The majority of protein phosphorylation research has been focused on serine, threonine and tyrosine that form acid-stable phosphomonoesters. However, protein histidine, arginine and lysine residues a...
Article
Regulation by phosphorylation is a well-established mechanism for controlling biological activity of proteins. Recently, phosphorylation of serine 124 in human thymidylate synthase (hTS) has been shown to lower the catalytic activity of the enzyme. To clarify a possible mechanism of the observed influence, molecular dynamics (MD), essential dynamic...
Article
Full-text available
Phosphorylation of proteins is an essential signalling mechanism in eukaryotic and prokaryotic cells. Although N-phosphorylation of basic amino acid is known for its importance in biological systems, it is still poorly explored in terms of products and mechanisms. In the present study, two MS fragmentation methods, ECD (electron-capture dissociatio...
Article
Thymidylate synthase (TS) was found to be a substrate for both catalytic subunits of human CK2, with phosphorylation by CK2alpha and CK2alpha' characterized by similar K(m) values, 4.6microM and 4.2microM, respectively, but different efficiencies, the apparent turnover number with CK2alpha being 10-fold higher. With both catalytic subunits, phospho...
Article
Full-text available
Thymidylate synthase (TS) may undergo phosphorylation as endogenous protein present in mammalian cells and as recombinant protein (corresponding to human, rat, mouse or Trichinella spiralis TS) expressed in bacterial cells. The phosphorylated, compared to non-phosphorylated, recombinant enzyme forms show decreased (at least by 3-fold) molecular act...
Article
Full-text available
Crystal structures of mouse thymidylate synthase (mTS), liganded with either 2'-deoxyuridine 5'-monophosphate (dUMP) or the sulfate anion, have been determined and deposited in Protein Data Bank under the accession codes 3IHH and 3IHI, respectively. The structures show a strong overall similarity to the corresponding structures of rat (rTS) and hum...
Article
Full-text available
Novel 15N-isotope enriched potassium and diammonium thiophosphoramidates were synthesized and their spectroscopic properties, along with reactivity towards several compounds, including histidine, thymidine, glucose and 2- deoxyribose are presented. The application of quantum mechanical DFT calculations for estimation of 31P NMR chemical shifts for...
Article
Novel N-15-isotope enriched potassium and diammonium thiophosphoramidates were synthesized and their spectroscopic properties, along with reactivity towards several compounds, including histidine, thymidine, glucose and 2-deoxyribose are presented. The application of quantum mechanical DFT calculations for estimation of P-31 NMR chemical shifts for...
Article
In search of an activity-preserving protein thiophosphorylation method, with thymidylate synthase recombinant protein used as a substrate, potassium thiophosphoramidate and diammonium thiophosphoramidate salts in Tris- and ammonium carbonate based buffer solutions were employed, proving to serve as a non-destructive environment. Using potassium pho...
Article
Oxidative stress is considered to be the main cause of diabetic complications. As the role of antioxidants in diabetes therapy is still underestimated, the aim of the present investigation was to study the antioxidative action of melatonin in comparison with N-acetylcysteine (NAC) under diabetic conditions. Alloxan-diabetic rabbits were treated dai...
Article
Full-text available
Thymidylate synthase purified from 5-fluoro-dUrd-resistant mouse leukemia L1210 cells (TSr) was less sensitive to slow-binding inhibition by 5-fluoro-dUMP than the enzyme from the parental cells (TSp), both enzyme forms differing also in sensitivity to several other dump analogues, apparent molecular weights of monomer and dimer, and temperature de...
Article
Full-text available
Crude extract specific activities of thymidylate synthase, dUTPase, thymidine kinase and dihydrofolate reductase were high during the development of Caenorhabditis elegans, the dauer larva activities being similar to those previously determined in Trichinella spiralis and T. pseudospiralis muscle larvae (with the exception of thymidine kinase, not...
Article
Full-text available
Effect of vanadyl acetylacetonate (VAc), tungstate and molybdate on gluconeogenesis has been studied in isolated hepatocytes and kidney-cortex tubules. In renal tubules of control and alloxan-diabetic animals, the rank order of the metal-compounds-induced (i) inhibition of glucose formation from alanine+glycerol+octanoate or aspartate+glycerol+octa...
Article
Full-text available
Diabetes-induced changes in glucose formation, intracellular and mitochondrial glutathione redox states as well as hydroxyl free radicals (HFR) generation have been investigated in rabbit kidney-cortex tubules. In contrast to renal tubules of control animals, diabetes-evoked increase in glucose formation in the presence of either aspartate+glycerol...

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