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Studium konformačních efektů vazby ligandu na proteinovou strukturu
Šefců, Oskar ; Novotný, Marian (advisor) ; Hexnerová, Rozálie (referee)
This bachelor thesis aims to provide a comprehensive overview of the effects of ligand binding on the 3D structure of proteins. The focus will be on examples where ligand binding causes a significant conformational change between the structure without the ligand (apo structure) and the structure with the ligand (holo-structure). The thesis will discuss various techniques used to determine the structural changes caused by ligand binding, including X-ray crystallography, NMR spectroscopy, and cryo-electron microscopy. Furthermore, the thesis will provide insight into the structural and functional implications of ligand-induced conformational changes in proteins. Overall, this thesis will serve as a resource for understanding the role of ligand binding in modulating the 3D structure of proteins. Keywords: apo, holo, ligand, conformational change, IDP
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Structural NMR studies of protein complexes
Hexnerová, Rozálie ; Veverka, Václav (advisor) ; Hrabal, Richard (referee) ; Hlouchová, Klára (referee)
Protein-protein interactions are involved in various biological processes and detailed characterization of their structural basis by the means of structural biology is often instrumental for rigorous understanding of underlying molecular mechanisms. This information is important not only for fundamental biology but also plays an important role in search for sites amenable for therapeutic intervention. Nuclear magnetic resonance spectroscopy is alongside X-ray crystallography and single-particle cryo-electron microscopy one of the key high-resolution techniques in structural biology. Although its applicability to larger systems has a well-known physical limit, it offers unique capabilities in addressing highly dynamic or inherently heterogeneous systems. In this doctoral thesis, the solution-based NMR approach was used for detailed structural characterization of selected biologically important proteins and their complexes that provided important insights into their biological roles. In three distinct projects, I (i) studied the relationship between the structural effects of particular modifications in the insulin-like growth factor II (IGF-II) and their selectivity to the insulin axis receptors; (ii) the specific binding mechanism of the SH3 domain from the Crk-associated substrate (CAS); (iii) and...
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NMR studies of metabolicaly active peptides
Hexnerová, Rozálie ; Tošner, Zdeněk (advisor) ; Obšil, Tomáš (referee)
The regulation of metabolic and mitogenic cellular processes is a complex system, depending on the precise function of several signalling cascades. One example is the insulin pathway, which is mediated by a group of three sequentially and structurally highly similar hormones (insulin, insulin-like growth factor (IGF) -I and -II) and their homologous tyrosine kinase receptors (IR-A, IR-B, IGF-1R). Such a high degree of homology leads to crosstalk in receptor communication, with each of the ligands triggering different biological responses. The design of insulin analogues activating primarily metabolic effects or IGF antagonists suppressing an unfavourable mitogenic response is one of the main goals in this research field, which can be facilitated by identification of the regions responsible for receptor binding. The work included in this thesis is focused on the effects on receptor interactions following the introduction of selected elements from the IGF-I primary sequence into the IGF-II molecule. In particular, these include a point mutation of Ser29 to Asn, an insertion of Gly-Ser after Arg34 , an insertion of Pro-Gln after Ser39 , or combination of both insertions. Although the IGF-II modifications described here negatively affected binding affinity towards IR-A, they did not enhance the IGF-1R...
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