Michał Błażej PonczekUniversity of Lodz · Department of General Biochemistry
Michał Błażej Ponczek
PhD DSc (dr hab. or dr. habil.) Biochemistry
Namra Fatima joined my lab as a PhD student at
www.uni.lodz.pl/biomedchem
Area: CryoEM structure of kininogen
About
88
Publications
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Introduction
Molecular evolution, phylogenetics, molecular modelling, docking, dynamics and bioinformatics in the field of biochemistry of proteins of hemostasis and drug design, with particular emphasis on the importance of contact proteases (FXI, FXII, PK) in thrombotic diseases. Simulations of ligand binding to proteins - molecular docking. Structural prediction, modelling, molecular dynamics and other analyses of proteins. Drug likeliness prediction. Structural biology - CryoEM - structure of kininogens.
Additional affiliations
June 2019 - July 2019
October 2008 - present
April 2008 - July 2008
Position
- Fellow
Description
- EMBO Short-Term Fellowship ASTF 83.00-2008
Education
March 2017 - March 2017
ideas4biology
Field of study
- Training course: NGS in the study of gene regulation
March 2017 - March 2017
ideas4biology
Field of study
- Training course: Introduction to processing and analyzing NGS data
February 2017 - September 2017
University of Lodz
Field of study
- Biochemistry and Bioinformatics
Publications
Publications (88)
Previous reports have noted that factor (F) XI and FXII and prekallikrein (the contact phase proteases) are absent in fish.
A broad survey of recently completed genomes was undertaken to find where during the course of vertebrate evolution these coagulation factors appeared.
BLAST searches were conducted for the various factors on genomes of lampre...
Protochordate genomes enable a prevalence of hemostasis evolution. Broad searches were performed for homologs of human serine proteases of hemostasis on the genomes of Branchiostoma floridae, Saccoglossus kowalevskii, and Strongylocentrotus purpuratus. Sequences were analyzed by multiple bioinformatic tools. The survey revealed numerous homologous...
Factor XI (FXI) is the zymogen of a plasma protease (FXIa) that contributes to hemostasis by activating factor IX (FIX). In the original cascade model of coagulation, FXI is converted to FXIa by factor XIIa (FXIIa), a component, along with prekallikrein and high-molecular-weight kininogen (HK), of the plasma kallikrein-kinin system (KKS). More rece...
Kininogens are multidomain glycoproteins found in the blood of most vertebrates. High molecular weight kininogen demonstrate both carrier and co-factor activity as part of the intrinsic pathway of coagulation, leading to thrombin generation. Kininogens are the source of the vasoactive nonapeptide bradykinin. To date, attempts to crystallize kininog...
Background
During plasma contact activation, factor XII (FXII) binds to surfaces through its heavy chain, and undergoes conversion to the protease FXIIa. FXIIa activates prekallikrein and factor XI (FXI). Recently, we showed that the FXII first epidermal growth factor (EGF1) domain is required for normal activity when polyphosphate is used as a sur...
This article presents the biochemical properties of poly(lactide)-zinc (PLA-Zn) composites obtained by DC magnetron sputtering of zinc onto melt-blown nonwoven fabrics. The biochemical properties were determined by the evaluation of the activated partial thromboplastin time (aPTT) and prothrombin time (PT). The antimicrobial activity of the PLA-Zn...
Kininogen wielkocząsteczkowy (HK), działając jako kofaktor krzepnięcia krwi w procesie
krzepnięcia przez kontakt na naładowanych ujemnie powierzchniach, wiąże prekallikreinę oraz
czynnik XI przy udziale czynnika XII, a dodatkowo służy jako źródło uwalniania bradykininy. Słabej
rozdzielczości obrazy cząsteczek zostały uzyskane wiele lat temu za pomo...
The paper presents the investigation of the biological properties of Poly(Lactide)—Copper
composite material obtained by sputter deposition of copper onto Poly(lactide) melt-blown nonwoven
fabrics. The functionalized composite material was subjected to microbial activity tests
against colonies of Gram-positive (Staphylococcus aureus), Gram-negative...
Background: Blackthorn flower (Prunus spinosa L.) is a traditional herbal remedy recommended for treating cardiovascular diseases (CVDs).
Aim: This in vitro study investigates the effects of flavonol and A-type procyanidin-rich blackthorn flower extracts on the hemostatic system, including the blood plasma coagulation cascade and platelet aggregati...
Alginate-based materials have gained significant attention in the medical industry due to their biochemical properties. In this article, we aimed to synthesize Cotton-Alginate-Copper Composite Materials (COT-Alg (−) Cu (2+)). The main purpose of this study was to assess the biochemical properties of new composites in the area of blood plasma coagul...
Factor XII (FXII), the zymogen of the plasma protease FXIIa, contributes to thrombo-inflammatory processes. As part of the kallikrein-kinin system, FXIIa converts prekallikrein to the protease kallikrein (PKa), which then cleaves high-molecular-weight kininogen (HK) to release the vasoactive peptide bradykinin. In the disorder hereditary angioedema...
Oral Communication Coagulation and Natural Anticoagulants
Contact Pathway: Structure and Function II
OC 70.2 - The first insight into the spatial structure of human kininogen by cryogenic electron microscopy and computational methods
Wednesday, June 28, 2023 10:30 – 10:45 ET Room: 516
Session Available As: Live-Stream and On-Demand
Presenting Autho...
Background: High molecular weight kininogen (HK) is a key cofactor for
appropriate assembly and activation of the contact system which binds
prekallikrein (PK) and Factor XI (FXI). The FXI and PK-HK interactions
mediate critical binding interactions that facilitate contact activation and
bradykinin generation.
Aims: To understand the utility of Alp...
Ethnopharmacological relevance:
Traditional medicine recommends the use of Rheum rhaponticum L. and R. rhabarbarum L. to treat over thirty complaints, including disorders related to the cardiovascular system such as heartache, pains in the pericardium, epistaxis and other types of haemorrhage, blood purification as well as disorders of venous circ...
Background:
Inflammation, endothelial dysfunction, and alterations in blood physiology are key factors contributing to atherosclerosis and other cardiovascular disorders. Hence, modulation of endothelial function and reducing its pro-inflammatory and pro-thrombotic activity is considered one of the most important cardioprotective strategies. This...
This preprint is currently under review in IJMS journal (https://www.mdpi.com/journal/ijms).
Please, do not send me any peer review offers.
Abstract:
Kininogens are multidomain glycoproteins found in the blood of most vertebrates. They are important in the blood coagulation cascade pathways - in intrinsic pathway activation leading to thrombin ge...
![Fig 1. LIGPLOT for 6U26 showing the active site pocket from PDBsum [71].](profile/Daniel-Hoessli/publication/353719353/figure/fig1/AS:1053512993628160@1628188479197/LIGPLOT-for-6U26-showing-the-active-site-pocket-from-PDBsum-71_Q320.jpg)
Proprotein convertase subtilisin/kexin type 9 (PCSK9) is one of the key targets for athero-sclerosis drug development as its binding with low-density lipoprotein receptor leads to ath-erosclerosis. The protein-ligand interaction helps to understand the actual mechanism for the pharmacological action. This research aims to discover the best inhibito...
Ethnopharmacological relevance
A wide range of traditional medicine applications of Uncaria tomentosa (Willd. ex Schult.) DC., commonly known as ‘vilcacora’ or ‘cat's claw’, includes blood purification, its anticoagulant properties and its use in haemorrhage therapy.
Aim of the study
Our work is devoted to the effects of ethanol and aqueous extrac...
The Pulmonaria species (lungwort) are edible plants and traditional remedies for different disorders of the respiratory system. Our work covers a comparative study on biological actions in human blood plasma and cyclooxygenase-2 (COX-2)-inhibitory properties of plant extracts (i.e., phenolic-rich fractions) originated from aerial parts of P. obscur...
https://worldwide.espacenet.com/patent/search/family/074186999/publication/PL236490B1?q=ap%3DPL426715%2A
Abstract: NOVELTY - Producing protein-nucleic complexes involves using blood coagulation contact proteins and obtaining purified nucleic acids. The nucleic acids are isolated from peripheral blood mononuclear cells (PBMCs) obtained by density g...
Abstract Number: PB0255
Theme: Coagulation and Natural Anticoagulants » Contact Pathway
Background: Whole genome sequences have facilitated reconstruction of the natural histories of complex processes, such as vertebrate blood coagulation (Figure).
Aims: To update and correct our prior work on the evolution of the kallikrein-kinin system (KKS) p...
Many natural coumarins and their chemically synthesized analogs and derivatives exert diverse properties, such as anticancer, antioxidant, anti-inflammatory, or anticoagulant, with the latter being of the utmost importance. The widely used warfarin, acenocoumarol, and phenprocoumon exert anticoagulant properties by inhibiting the vitamin K epoxide...
Sposób wytwarzania kompleksów białkowo-nukleinowych z udziałem białek kontaktu krzepnięcia krwi oraz uzyskiwania z nich oczyszczonych kwasów nukleinowych, znamienny tym, że kwasy nukleinowe izoluje się z jednojądrzastych komórek krwi obwodowej (PBMC) otrzymanych przez wirowanie krwi w gradiencie gęstości, i poddaje się je reakcji z osoczem uzyskiwa...
The aim of this study was to determine the cytotoxic effect of 3-arylidenechromanone (1) and 3-arylideneflavanone (2) on HL-60 and NALM-6 cell lines (two human leukemia cell lines) and a WM-115 melanoma cell line. Both compounds exhibited high cytotoxic activity with higher cytotoxicity exerted by compound 2, for which IC50 values below 10 µM were...
Project “Support for European Union action in the field of CBRN security managers education” SE-CBRN-URE is funded by European Commission, The Directorate-General for Migration and Home Affairs (DG HOME) from Internal Security Fund – Police, call “Implementation of the EU CBRN Action Plan, the EU Action Plan on enhancing the security of explosives...
Plasmin (EC 3.4.21.7) is a key enzyme of the fibrinolytic system, responsible for the degradation of fibrin clot and maintaining blood fluidity. Hence, alterations of the fibrinolytic capacity of blood plasma may contribute to thrombotic or bleeding complications. The aim of this study was to determine effects of a bufadienolide-rich fraction, isol...
Blood coagulation is caused, i.a., by proteins called coagulation factors. Excessive clotting leads to blood clots and blockages in the blood vessels and threatens death. Clots are often initiated by a group of clotting proteins, which are called contact factors (factor XI, factor XII, prekallikrein, high molecular weight kininogen). Contact factor...
Background:
Scientists still look for new drugs, which have anticoagulant properties. This is so important because existing anticoagulant drugs give many side effects, for example major bleeding. In this study we examined nine coumarin derivatives - candidates to be future antithrombotic drugs, which were synthetized and crystallized in our previo...
This paper examines the cytotoxic effect of nine compounds with spiropyrazoline structures, and determines the reaction mechanism between diazomethane and selected benzylideneflavanones, their lipophilicity, and their binding ability to human serum albumin. The cytotoxic effect was determined on two human leukaemia cell lines (HL-60 and NALM-6) and...
Thrombin is an active plasma coagulation factor II, critical for the formation of fibrin clot during blood coagulation. For that reason, this protein is also a crucial target for different anti-thrombotic therapies. The work is based on in vitro evaluation of the inhibitory effect of bufadienolide-rich fraction, isolated from roots of Kalanchoe dai...
Intensive genetic selection has improved productive traits in poultry and contributed to changes in systemic metabolism; however, their blood coagulation processes have received little study. The precise physiological mechanisms of haemostasis in birds remain poorly understood, but blood clotting is believed to be governed by an extrinsic tissue fa...
The tissue factor (TF) – tissue factor pathway inhibitor (TFPI) axis plays a major role in hemostasis. Disorders of the coagulation system are commonly diagnosed with the help of screening tests such as prothrombin time (PT), activated partial thromboplastin time (aPTT), and plasma fibrinogen concentration (PFC). However, the effect of prebiotics o...
Blood coagulation factor XI is significant protein of haemostasis and thrombosis forming dimers through N-terminal apple 4 domains. Known crystal and NMR structures of apple 4 dimers are slightly different. Therefore, dynamics of dimeric blood coagulation factor XI seems to be interesting phenomenon as crystal and NMR structures show differences, a...
Coagulation factor XI is present in blood plasma as the zymogen, like other serine proteases of hemostatic system, but as the only coagulation factor forms 140–160 kDa homodimers. Its activation is induced by thrombin, and a positive feedback increases the generation of the extra thrombin. Experimental and clinical observations confirm protective r...
Series of new coumarin derivatives with di- or trimethoxybenzylamine moiety in C-3 position were synthesized. The structures of all obtained compounds were characterized by IR, 1H NMR, MS and elemental analysis. Two structures of coumarin were determined by X-ray crystallography. Hirshfeld surface analysis has been employed in order to study interm...
Blood coagulation factor XI (FXI) is a protein regarded as an important risk factor of thrombosis and a
medication target in humans. [1] It consists of four N-terminal apple domains (A1, A2, A3 and A4) and one Cterminal
serine protease domain (SP). Two polypeptide chains form homodimer through A4 domains. The
structure of the human dimer was solved...
The aim of the present study was the investigation of peroxynitrite (ONOO(-)) effects on fibrinolysis in vitro and in silico. The exposure of human plasminogen to ONOO(-) (10-1000μM) resulted in a decrease of t-PA-induced amidolytic activity of plasmin; the inhibitory effect was associated with the increasing level of 3-nitrotyrosine in plasminogen...
Proteolytic enzymes, known also as the proteases,
proteinases or peptidases, belong to the class
of hydrolases involved in hydrolytic degradation of
peptide bonds. These enzymes have been identified
in both prokaryotic and eukaryotic cells. Typical human
genome contains about 2% of the genes that
are responsible for encoding of proteolytic enzymes....
Matricaria chamomilla L. (MC), a member of the Asteraceae family, is one of the oldest medicinal plants, widely used worldwide for a variety of healing applications. Its recommendations, derived from both traditional and modern medicine, include numerous disorders such as inflammation, ulcers, wounds, gastrointestinal disorders, stomach each, phary...
The coagulation factor XI (FXI) is a novel protein in vertebrate evolution, present only in mammals offering an extra way for more effective blood clotting. The consequence of an increased risk of thrombosis is a grim side effect. FXI takes part in intrinsic blood coagulation after factor XII (FXII) activation on negatively charged contact surfaces...
Thrombin, also known as an active plasma coagulation factor II, belongs to the family of serine proteases and plays a crucial role in blood coagulation process. The process of thrombin generation is the central event of the hemostatic process and regulates blood coagulant activity. For this reason, thrombin inhibition is key to successful novel ant...
Blood coagulation consists of series of zymogens which can be converted by limited proteolysis to active enzymes leading to the generation of thrombin and conversion of fibrinogen into fibrin by this enzyme. The activated factor X (FXa) forms prothrombinase complex on phosphatidylserine containing surface which is responsible for conversion of prot...
Platelets are the smallest, depleted of nucleus blood cells which contain a typical cellular organelles including the mitochondria, so that have active metabolism. Platelets possess the highly organized cytoskeleton, specific secretory granules and unique membrane receptors system responsible for their high reactivity. The key role of blood platele...
Subjects of bovine and porcine flocks are sometimes susceptible to death before time of slaughter, and some of those deaths may be due to cardiovascular problems connected with stress. The role of oxidative stress in farm animals is yet unexplored. Human fibrinogen seems to be highly susceptible to nitration. Peroxynitrite produced from superoxide...
LPS (lipopolysaccharide) induces platelet activation and is a well-known fundamental agent of septic shock and disseminated intravascular coagulation (DIC). Biological activity of (1→3)-β-d-glucan is related due to its anti-inflammatory, antioxidant, and antitumor properties. We focus our attention on the (1→3)-β-d-glucan (antiplatelet) properties....
Participation of fibrin, fibrinogen, and their degradation products in pathogenesis and progression of cancer may lead to complications of thromboembolic events. The tumor may be a source of fibrinogen. Fibrinogen inside the tumor is one of the factors of its growth and metastasis. Fibrinogen, fibrin and their degradation products possess proinflam...
A unique mechanism of clot formation evolved in time of the emergence of vertebrates, probably more than 500 million years ago. In the classical cascade of blood clotting thrombin formation may be initiated by two overlapping coagulation pathways – extrinsic and intrinsic pathway. The common target for these alternative routes is the initiation of...
Fibrinogen (Fg) also known as coagulation factor I represents about 4% of the total human plasma proteins. The main function of Fg is its involvement in last phase of blood coagulation cascade, when thrombin-induced conversion of dissolved plasma fibrinogen into an insoluble fibrin clot occurs. The reaction of fibrinogen with peroxynitrite causes b...
Platelets are the smallest, unnucleated blood cells that play a key role in maintaining normal hemostasis. In the human body about 1x1011 platelets are formed every day, as a the result of complex processes of differentiation, maturation and fragmentation of megakaryocytes. Studies done over 4 decades ago demonstrated that circulating in blood matu...
Thrombin is a serine protease that cleaves the peptide bonds in proteins located on the carboxyl side of arginine. Thrombin plays a central role in thromboembolic diseases, which are the major cause of mortality. The aim of the study was to estimate the effects of plant extracts on proteolytic properties of thrombin. Thrombin was incubated with pol...
Recently performed whole genome sequencing of exponents
of primitive chordates like amphioxus Branchiostoma
floridae and sea squirt Ciona intestinalis, hemichordates like
acorn worm Saccoglossus kowalevskii and echinoderms such
as sea urchin Strongylocentrotus purpuratus enables moving
back in examination of evolution of hemostasis.
The purpose of...
Appendix 1. Sequences (Fig. 2), sequences and results of phylogenetic analysis (Fig. 3). Supplementary material 1
Oxidative stress, vascular inflammation, endothelial dysfunction plays a crucial role in the pathogenesis of cardiovascular diseases. The aim of our in vitro study was to examine the antioxidative properties of grape seed extract, and its potential protective effect on the haemostatic function of human fibrinogen under oxidative stress conditions,...
Fibrinogen appears to be particularly sensitive to toxic action of peroxynitrite; a potent oxidizing and nitrating species. An increased nitration of fibrinogen has been reported in cardiovascular diseases. The defense mechanisms against PN are crucial for complex hemostasis process. Flavonoids have antioxidative properties and could protect biomol...
Oxidative stress plays an important role in multiple sclerosis (MS).
The present study was designed to evaluate the modifications of plasma proteins by estimation markers of oxidative/nitrosative stress: carbonyl groups and 3-nitrotyrosines (3-NT) levels in relapsing-remitting (RR) (n=10) and secondary progressive (SP) (n=10) clinical course of mul...
Thrombin is plasma serine protease generated in the blood coagulation cascade. Active form of
human thrombin: α-thrombin is a 36 kDa molecule consisting of 2 polypeptide chains (A and B) covalently
linked by a single disulfide bond. Thrombin is mostly associated with blood coagulation and fibrinolysis. However, thrombin is also able to induce biolo...
As demonstrated in recent years, one of the major factors of oxidative stress, generated in the circulatory system, in both acute and chronic pathological conditions, is peroxynitrite (ONOO –). Peroxynitrite is a strong biological oxidant and nitrating compound, generated in vivo from a rapid reaction of two relatively
less reactive, but commonly f...
Lots of plants belonging to Asteraceae family are very popular in folk medicine in Poland. These plants are also known as being rich in acidic polysaccharides, due to the presence of hexuronic acids or its derivatives. Our preliminary experiments have shown that the extract from Conyza canadensis L. possesses various biological activity, including...
Oral hormone therapy (HT) and menopausal age are both prothrombotic risk factors. The aim of our study was to compare the hemostatic parameters in plasma of postmenopausal women after 6 months of oral HT with parameters of control (without treatment) postmenopausal women.
Twenty-seven postmenopausal women were treated with 17β-estradiol (1 mg) and...
Hormone therapy (HT) can be prothrombotic risk factor. We compared the effects of oral HT (o-HT) and transdermal HT (t-HT) on the kinetic of clot formation and fibrinolysis in postmenopausal women after 6 months HT using a multiparameter test. We observed that after HT, the level of fibrinogen was higher than in controls (Fg 3.12 g/l vs. 4.24 g/l (...
The extremely complicated systems of proteins are a result of many series of duplications and shuffling
of domains in genomes of predecessors of nowadays living creatures. Fibrinogen, a key blood clotting protein, is characteristic only for vertebrates. The protein could not be found in chordates like lancelet or sea squirt by biochemical nor bioin...
C-terminals of amino acid sequences that are homological to fibrinogen chains, together belong to family of FRED domains. FRED domains are engaged in protein – protein interactions, like in fibrinogen and angiopoietins or bind carbohydrate, like in mammal ficolins. FRED domain spread between mentioned proteins by gen duplications and exon shuffling...
Enterprises of whole genome sequencing together with information technology progress enable reconstruction of blood clotting evolution by bioinformatic methods. It together offers a base to conclude that the contact phase of vertebrate blood coagulation is evolutionary young and shaped merely before divergence of marsupial and placental mammals. Am...
The intrinsic phase of blood coagulation seems to be evolutionary
young and shaped merely in marsupial and placental
mammals. Amphibians, birds and platypus own a
single gene corresponding to the predecessor of factor XI
(FXI) and prekallikrein (PK) as revealed by bioinformatic
genome searches. The opossum has both PK and FXI like
eutherian mammals...
Blood clotting and fibrinolysis proteins of mammals and other higher vertebrates appear to be a result of gene duplications, divergence and domain shifting. Extrinsic pathway, important in physiologic coagulation in human, looks to be simpler in lampreys comparing with jawed vertebrates. On the other hand, intrinsic pathway, significant in patholog...
The effect of nitronium ion on nitration, carbonylation and coagulation of human fibrinogen (Fg) in vitro was investigated. We observed that nitration of tyrosine, induced by NO2BF4 (0.01 mmol/l), was increased. No changes in carbonylation by NO2BF4 (0.01 mmol/l) were noticed. Mentioned alterations were associated with amplified coagulation of Fg....
Based on previous studies suggesting that fibrinogen (Fg) might be a potential target for peroxynitrite (PN) action in plasma, we investigated the effects of PN on structure and hemostatic function of Fg in vitro. Using fluorescence and spectrophotometric methods, we estimated that about 0.5, 2 and 8 tyrosine residues per molecule were nitrated fol...
Resveratrol (3,4',5-trihydroxystilbene) has a very broad range of biological properties, including antiplatelet and antioxidative activity. We investigated in vitro the effect of resveratrol on carbonylation of proteins (indicators of oxidative stress) in blood platelets treated with peroxynitrite (ONOO(-)), a strong biological oxidant and inflamma...
The protective effects of resveratrol (3, 4', 5-trihydroxystilbene; present naturally in different plants) against the oxidative/nitrative damage of human plasma proteins induced by peroxynitrite (ONOO-) were studied and compared with those of deferoxamine (DFO; a natural siderophore isolated from Streptomyces pilosus), which is a typical and well-...
Free radicals and reactive oxygen or nitrogen species generated during oxidative stress and as by-products of normal cellular metabolism may damage all types of biological molecules. Proteins are major initial targets in cell. Reactions of a variety of free radicals and reactive oxygen and nitrogen species with proteins can lead to oxidative modifi...
Questions
Questions (3)
I am looking for an open bioinformatic program or script with the option of quick analyzing the presence or absence of nonsynonymous SNPs in the NGS results of amplicons of known proteins in a particular human individuals. The program of course may include mapping to the reference genomes but in principle it should detect known SNPs by analyzing the nucleotide sequence and finding a substitution in a codon causing a change in a known SNP position (triggering mutation to another amino acid). Mainly known substitutions are important, however detection of novel would be optional with mapping. I possibly would appreciate pointing to a few programs to fix them with a script. And it's not about dbSNP on NCBI or any other.
Is there any way in Europe to get a small amount of frozen citrate plasma (several microliters should be enough) of platypus and echidna from Australia?
The research would involve cross-check reaction of some monotreme plasma proteins on antibodies against human plasma proteins by western-blotting.
If anyone has an access to the animals and knows how to organize such matter I would be grateful for personal contact.
