National Repository of Grey Literature 36 records found  1 - 10nextend  jump to record: Search took 0.00 seconds. 
Study of naphthalene access pathways to cytochrome P450 1A2.
Martinka, Jakub ; Jeřábek, Petr (advisor) ; Kulhánek, Petr (referee)
Cytochrome P450 1A2 is a human liver enzyme of a hemoprotein nature that belongs to the evolutionarily ancient group of cytochromes P450. Cytochrome P450 substrates include a wide range of drugs and most procarcinogens, making it a crucial enzyme for the study of carcinogenesis. The main reaction catalyzed by cytochrome P450 1A2 is monooxygenation, in which an oxygen atom is incorporated into a substrate molecule. This reaction takes place at an active site which, in the case of published structure of cytochrome P450 1A2, is buried in the core of the catalytic domain without an accessible tunnels. Molecular modeling techniques allow the study of dynamic phenomena in large systems and are therefore also suitable for simulations of the transport of substrate molecules to the active site. The tunnels are being made accessible due to structural fluctuations. In this work, molecular modeling techniques were used to study the pathways that the naphthalene molecule uses to enter the active site of cytochrome P450 1A2. A system consisting of cytochrome P450 1A2 anchored in a phospholipid membrane, water, ion and naphthalene molecules was simulated. The simulations yielded trajectories with a total length of 8 µs and the analysis identified seven tunnels that can be used to transport substrates....
Biochemical characterization of a model heme sensor protein
Tajovská, Eva ; Martínková, Markéta (advisor) ; Jeřábek, Petr (referee)
Hemoproteins play a lot of important roles within the living organism. One of these being the sensor function - heme sensor proteins are able to detect the changing concentration of heme in organisms. Heme itself serves as a signalling molecule for these proteins. Heme-based gas sensor proteins use a biatomic gas molecule as a signalling molecule. Signal transduction begins once the gas molecule is bound to the heme molecule which is already tightly bound in the protein sensing domain. Both these types of signalling regulate a number of physiological processes in the prokaryotic and eukaryotic organisms. The theoretical part of the bachelor thesis summarizes recent scientific studies on heme sensor proteins, while the experimental part focuses on the properties of a specific model sensor hemoprotein. A direct oxygen sensor from E. coli (EcDOS) was selected as a model protein. Furthermore, the thesis deals with a truncated form of the EcDOS protein, an isolated sensor domain with a PAS structure (EcDOS-PAS). The experimental part aimed at expressing and isolating of both mentioned proteins from E. coli BL-21 (DE3) cells. Finally, both the EcDOS and EcDOS-PAS proteins were preliminarily characterised and their properties compared. The yield of the EcDOS-PAS was several times higher than the yield of...
Effect of tyrosine kinase inhibitor cabozantinib and cytotoxic alkaloid ellipticine on expression and activity of cytochromes P450 1A1, 1A2 and 1B1
Měkotová, Barbora ; Dračínská, Helena (advisor) ; Jeřábek, Petr (referee)
In recent years, tyrosine kinase inhibitors have been more and more used for the targeted cancer therapy, due to their ability to disrupt intracellular signalling pathways associated with the development of tumours. Cabozantinib is the tyrosine kinase inhibitor which has been approved for the treatment of thyroid cancer and it is also effective against several other types of cancer. However, multiple drugs combination is often used in anticancer therapy, which may result in their cytochrome P450-mediated interactions. Although this may affect the therapeutic effect of the drugs and cause adverse effects on the organism, very little is known about the effect of cabozantinib on biotransformation enzymes. Therefore, the effect of cabozantinib not only alone but also in combination with the known cytostatic ellipticine on the expression and the activity of cytochromes P450 1A1, 1A2 and 1B1 in rat liver and kidney in vivo was studied in this work. The gene expression was determined by quantitative PCR, the amount of protein was studied by Western blotting and consecutive immunodetection. The enzyme activity was studied using specific marker reactions, 7-ethoxyresorufin O-deethylation for CYP1A1, 7-methoxyresorufin O-demethylation for CYP1A2 and 17β-estradiol 4-hydroxylation for CYP1B1. Our results...
Modeling of an influence of a phospholipid membrane composition on the structure and dynamics of cytochromes P450s.
Gücklhorn, David ; Jeřábek, Petr (advisor) ; Kulhánek, Petr (referee)
Cytochrome P450 1A2 is one the most important enzymes that take part in phase I of biotransformation of xenobiotics in human body. This enzyme is anchored in membrane via transmembrane α-helix. Composition of the phospholipid membrane can affect structure and dynamics of this enzyme. In this thesis optimized full-length all-atom model of cytochrome P450 1A2 in POPC (1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine) membrane was created based on crystal structure of catalytic domain of this enzyme. Methods of molecular dynamics were used for creation and optimization of the model which contained parts with unknown structure. The optimized model was subjected to thorough analysis of its structure and dynamics and compared to a similar model with DLPC (1,2-dilauroyl-sn-glycero-3- phosphocholine) membrane. The results show that the composition of the membrane significantly affects dynamics of transmembrane domain and its contact with catalytic domain. Usage of the thicker POPC membrane resulted in smaller contact between both domains which caused partial emergence of the catalytic domain from membrane. Penetration of palmitoyl chain of POPC into tunnel 2f was observed in one the trajectories. Analysis of pathways to active site of cytochrome P450 1A2 and the influence of the membrane composition on...
Deformation, metamorphism and metasomatism in the Gemer-Vepor Contact Zone in the Western Carpathians and the possible links to the Greywacke Zone in the Eastern Alps
Novotná, Nikol ; Jeřábek, Petr (advisor) ; Plašienka, Dušan (referee) ; Schuster, Ralf (referee)
The studied area extends from the Ochtiná Unit in Western Carpathians to the Veitsch Nappe Eastern Alps. The thesis represents a complex multidisciplinary work that combines the structural analysis, petrology and geochronology. The three main objectives of this thesis: reevaluation of the structure, deformation and metamorphic records, and original position of the Ochtiná Unit, understanding the distinct metasomatic processes recorded along the contact of two major units of the Central Western Carpathians - in the Gemer-Vepor Contact Zone - and their relation to distinct tectono-metamorphic events, testing the possible links between the Ochtiná Unit in the Gemer-Vepor Contact Zone of the Western Carpathians and the Veitsch Nappe in the Greywacke Zone of the Easten Alps, both well known for the Lower Carboniferous shale/schist sequence accompanied by the abundant presence of magnesite ore bodies. Keywords: Central Western Carpathians, Greywacke Zone, Ochtiná Unit, Veitsch Nappe, U-Pb zircon dating, Phase equilibrium modelling
Deformation history and decomposition of ternary feldspar in the proto-phase of the Blanský les felsic granulite evolution
Jirků, Markéta ; Jeřábek, Petr (advisor) ; Závada, Prokop (referee)
This diploma thesis deals with the oldest recognized deformation microstructure of felsic granulites of Blanský les (southern Bohemian Massif) in order to understand their lower crustal deformation history later altered during exhumation. Moreover, the study is focused on decomposition of ternary feldspars in the proto-phase of evolution of granulite microstructure. Based on the structural and microstructural analyses of the less developed cleavage I. and the more developed cleavage II., it was possible to distinguish between two deformation structures. The S1 is defined by compositional banding of alternating quartz bands with bands rich in plagioclase, garnets and with porphyroclasts of alkaline feldspars. The S1 cleavage is transposed into the S2 cleavage. During intense reworking of S1 into S2, the quartz bands were decomposed and recrystallized into the ribbons. The feldspar thermometry of the cleavage I. and II. allowed to distinguish the three stages of decomposition of feldspars. A continuous temperature decrease was observed as reflected by the individual microstructures. The quantitative microstructural analysis indicate the shape preferred orientation of the grain boundaries of two-feldspar matrix. The shape preferred orientation of cleavage I. is controlled by the albite rim, however after its...
Influence of degassing parameters on quality of Al castings
Jeřábek, Petr ; Horenský, Jiří (referee) ; Vašťák, Patrik (advisor)
This master’s thesis is focused on optimalization of degassing parameters in the foundry plant and effect of these parameters on mechanical properties of Al-Si alloys. In practical part is used factorial experiment to research effect of degassing parameters on mechanical properties and dichte index. After optimalization the new process is validated by comparing with the previous one. This experiment was taken on AlSi7Mg0,6 alloy in foundry plant MESIT foundry, a.s.

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1 JEŘÁBEK, Přemysl
4 Jeřábek, Pavel
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