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Biogenesis and function of nuclear iron-sulfur proteins
Panova, Ekaterina ; Benda, Martin (advisor) ; Smutná, Tamara (referee)
Iron-sulfur clusters are important inorganic cofactors of many cellular reactions, including those that occur in the nucleus. Nuclear iron-sulfur proteins play an important role in DNA replication, genome repair, and maintenance of genome stability. The biosynthesis of these iron-sulfur clusters is initiated in the mitochondria by the iron-sulfur cluster assembly pathway (ISC), continues in the cytosol by the cytosolic iron-sulfur cluster assembly pathway (CIA), and ends with the incorporation of the clusters into target apoproteins such as polymerases, primases, helicases, endonucleases, or glycosylases. This bachelor thesis summarizes current knowledge about the pathways of iron-sulfur cluster biosynthesis, the functions of nuclear iron-sulfur proteins, and the role of the clusters in these proteins, including the phenotypes and clinical manifestations caused by the absence of iron-sulfur clusters. Keywords: iron-sulfur clusters, metalloproteins, nucleus, DNA replication, DNA repair
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Modelling of the interaction of proteins and peptides with metal ions
Gutten, Ondrej ; Konvalinka, Jan (advisor) ; Obšil, Tomáš (referee)
Modelling of interactions of proteins and peptides with metal ions Ondrej Gutten - Diploma thesis Keywords: Metalloproteins, metal ion selectivity, in silico prediction Abstract: An approach for in silico prediction and estimation of selectivity properties of metal-binding peptides is suggested. An in-depth analysis is performed to disclose the justifiability and limitations of this approach. The study is divided into three parts. First part investigates the soundness of two quantum chemical methods (MP2 and DFT) for their use in the set-up quest. The testing includes comparison with CCSD(T), effect of basis selection, performance of the two methods in geometry optimizations and effect of implicit solvent model. Second part foreshadows the approach of searching for a metal selective peptide by thoroughly investigating the ability of simple representative systems, derived from their metalloprotein templates, to retain the property of interest. Final part describes the initial step of extensive combinatorial approach towards examination of vast number of simple systems that represent metal-binding sites, and which are to be used for prediction of metal-selectivity through exploitation of the described approach and, ultimately, to the de novo design of metalloproteins with desired properties.
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Characterization of Glutamate Carboxypeptidase II, its Close Homologs and their Interaction with Ligands
Tykvart, Jan
Cancer, group of diseases characterized by an uncontrolled cell growth, represents one of the great challenges of modern clinical research. Currently, the standard treatment of the cancer disease relies mainly on the whole body exposition to various factors, which targets the dividing cells, combined with surgical resection of the tumor. Unfortunately, this treatment is sometimes accompanied by numerous severe side-effects (e.g., nausea, loss of hair, infertility etc.). Therefore, in the past 40 years enormous resources and effort have been invested into finding a way how to specifically target and destroy the cancerous cells. This goal has been primarily addressed by the search for molecules, mainly proteins, which are predominantly expressed in the cancerous tissues compared to the healthy cells. Glutamate carboxypeptidase II (GCPII), also known as prostate specific membrane antigen (PSMA), represents such a target since it is highly expressed in a prostate carcinoma as well as in a solid tumor neovasculature. Additionally, GCPII is widely used as a model target molecule for proof-of-principle studies on targeted drug delivery. GCPII thorough biochemical characterization is essential for its appropriate use. Therefore, our laboratory has been investigating GCPII from various perspectives for more...
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Characterization of Glutamate Carboxypeptidase II, its Close Homologs and their Interaction with Ligands
Tykvart, Jan
Cancer, group of diseases characterized by an uncontrolled cell growth, represents one of the great challenges of modern clinical research. Currently, the standard treatment of the cancer disease relies mainly on the whole body exposition to various factors, which targets the dividing cells, combined with surgical resection of the tumor. Unfortunately, this treatment is sometimes accompanied by numerous severe side-effects (e.g., nausea, loss of hair, infertility etc.). Therefore, in the past 40 years enormous resources and effort have been invested into finding a way how to specifically target and destroy the cancerous cells. This goal has been primarily addressed by the search for molecules, mainly proteins, which are predominantly expressed in the cancerous tissues compared to the healthy cells. Glutamate carboxypeptidase II (GCPII), also known as prostate specific membrane antigen (PSMA), represents such a target since it is highly expressed in a prostate carcinoma as well as in a solid tumor neovasculature. Additionally, GCPII is widely used as a model target molecule for proof-of-principle studies on targeted drug delivery. GCPII thorough biochemical characterization is essential for its appropriate use. Therefore, our laboratory has been investigating GCPII from various perspectives for more...
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Characterization of Glutamate Carboxypeptidase II, its Close Homologs and their Interaction with Ligands
Tykvart, Jan ; Konvalinka, Jan (advisor) ; Obšil, Tomáš (referee) ; Pavlíček, Jiří (referee)
Cancer, group of diseases characterized by an uncontrolled cell growth, represents one of the great challenges of modern clinical research. Currently, the standard treatment of the cancer disease relies mainly on the whole body exposition to various factors, which targets the dividing cells, combined with surgical resection of the tumor. Unfortunately, this treatment is sometimes accompanied by numerous severe side-effects (e.g., nausea, loss of hair, infertility etc.). Therefore, in the past 40 years enormous resources and effort have been invested into finding a way how to specifically target and destroy the cancerous cells. This goal has been primarily addressed by the search for molecules, mainly proteins, which are predominantly expressed in the cancerous tissues compared to the healthy cells. Glutamate carboxypeptidase II (GCPII), also known as prostate specific membrane antigen (PSMA), represents such a target since it is highly expressed in a prostate carcinoma as well as in a solid tumor neovasculature. Additionally, GCPII is widely used as a model target molecule for proof-of-principle studies on targeted drug delivery. GCPII thorough biochemical characterization is essential for its appropriate use. Therefore, our laboratory has been investigating GCPII from various perspectives for more...
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Modelling of the interaction of proteins and peptides with metal ions
Gutten, Ondrej ; Konvalinka, Jan (advisor) ; Obšil, Tomáš (referee)
Modelling of interactions of proteins and peptides with metal ions Ondrej Gutten - Diploma thesis Keywords: Metalloproteins, metal ion selectivity, in silico prediction Abstract: An approach for in silico prediction and estimation of selectivity properties of metal-binding peptides is suggested. An in-depth analysis is performed to disclose the justifiability and limitations of this approach. The study is divided into three parts. First part investigates the soundness of two quantum chemical methods (MP2 and DFT) for their use in the set-up quest. The testing includes comparison with CCSD(T), effect of basis selection, performance of the two methods in geometry optimizations and effect of implicit solvent model. Second part foreshadows the approach of searching for a metal selective peptide by thoroughly investigating the ability of simple representative systems, derived from their metalloprotein templates, to retain the property of interest. Final part describes the initial step of extensive combinatorial approach towards examination of vast number of simple systems that represent metal-binding sites, and which are to be used for prediction of metal-selectivity through exploitation of the described approach and, ultimately, to the de novo design of metalloproteins with desired properties.
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