Global ETD Search
Search theses and dissertations gathered from participating repositories worldwide. Every result links back to the library that holds it. No account is needed.
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Showing 1 to 20 of 38 for “"allosteric regulation"”.
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Understanding the effect of allosteric regulation of Aurora kinases on inhibitor binding
… overexpression is associated with mitotic dysregulation and tumorigenesis. Many ATP-competitive inhibitors of Aurora kinases have been developed and are in various phases of clinical trials. However, the lack of correct stratification of the patient population along with a poor understanding …
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Structural studies of allosteric regulation in the class Ia Ribonucleotide reductase from Escherichia coli
… and [alpha]2 contains the active site and two allosteric effector binding sites. Allosteric control of RNR fine-tunes both the relative ratios (via substrate specificity regulation) and the total amount (via activity regulation) of deoxyribonucleotides (dNTPs) in the cell. The molecular basis …
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Interrogation of the human glutamate dehydrogenase antenna to elucidate its role in allosteric regulation and disease
… organisms, but only GDH from animals is highly allosterically regulated by a wide array of metabolites. The importance of this regulation is made evident by hyperinsulinism/hyperammonemia syndrome (HI/HA), where mutations cause GDH hyperactivity. Since only allosterically regulated forms of the …
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Biophysical Investigation into the Protein Dynamics Governing the Allosteric Regulation of Plant and Animal 15-Lipoxygenases
… of these enzymes, research has turned to allosteric regulation, which is the focus of this Thesis. Previously, the allosteric regulation of a model plant 15-LOX, soybean lipoxygenase-1 (SLO), has been characterized using hydrogen-deuterium exchange mass spectrometry (HDX-MS), revealing …
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Discovery and investigation of the novel overall activity allosteric regulation of the Bacillus subtilis class Ib ribonucleotide reductase
… of two subunits: a houses the catalytic and allosteric effector binding sites, and p houses a catalytically essential dimanganic-tyrosyl radical (Mn(III)2-Y*). The allosteric regulation of lb RNR activity has only been studied with the Salmonella enterica enzyme, which exhibits substrate …
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The role of the N domain in substrate binding, oligomerization, and allosteric regulation of the AAA+ Lon protease
… and a peptidase domain. Degron binding allosterically regulates Lon activity and can shift Lon into conformations with higher or lower protease activity, but the mechanistic basis of this regulation is unknown. The low-protease conformation of Lon may serve as a chaperone. In Chapter 2, …
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Dissection of spatiotemporal intracellular signaling using engineered chemical and genetic tools
… are propagated through networks that rely on allosteric regulation, post-translational modifications, or other mechanisms for modulating signaling protein activity. Scientists seeking to engineer systems that mimic endogenous pathways must be able to control and precisely tune the …
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The Development and Application of Methods to Study the Evolution of Specificity, Allostery, and RNA -Protein Interactions in Translation
… the mechanism and identify residues critical for allosteric regulation in a bacterial glutamyl tRNA-synthetase (GluRS):tRNA complex. In addition, our evolutionary analysis shows that the ancestral core of the class I AARS family consists only of the catalytic domain while the anticodon binding …
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Search for Insulin Secretion Modulators, Novel Functions of WNK Signaling and Intramolecular Signal Transduction in ERK2
In this dissertation, the regulation of insulin secretion from pancreatic beta cells, WNK1 pathway involvement in cell migration, angiogenesis, breast cancer, and other processes, as well as ERK2 intradomain communication are discussed. Each chapter is dedicated to a separate project, but the …
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Structural And Functional Studies On Thrombin Allostery
Thrombin is an allosteric serine protease endowed with important physiological functions in the blood. Once activated, α-thrombin plays procoagulant, prothrombotic, and anticoagulant functions in blood. Its important role in blood coagulation can be emphasized by the fact that thrombin interacts …
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The Effects of 3-Phosphoglycerate and Other Metabolites on the Activation of AMP-Activated Protein Kinase by LKB1/STRAD/MO25
… skeletal muscle contraction may be regulated by allosteric mechanisms. In this study we tested an array of metabolites including glucose-6-phosphate (G6P), fructose-6-phosphate (F6P), fructose 1,6-bisphosphate (F1,6-P2), 3-phosphoglycerate (3PG), glucose-1-phosphate (G1P), …
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Investigating the Structure and Function of IGP Synthase
… in all known GATs, may serve as a model of allosteric regulation for the entire enzyme family. Through the use of SMD simulations to induce ligand dissociation and additional experimental kinetic assays, we elicited evidence of the allosteric effect in IGP synthase and found a coupled motion …
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Pyruvate dehydrogenase activity in response to skeletal muscle contraction at two stimulation frequencies in pyruvate dehydrogenase kinase 2 knockout mice
… due to its phosphorylation site specificity and allosteric regulation. These results suggest that the site specificity and allosteric regulatory properties of the individual PDK isoforms are more important than total PDK activity in determining transformation of the complex and PDHa activity …
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Biophysical studies of the allosteric regulatory mechanism of Syk tandem SH2 domains interacting with immunoreceptor tyrosine-based activation motifs
… and the detailed mechanism of this long-distance allosteric regulation is largely unknown.</p> <p>A series of biophysical experiments, such as NMR and ITC, have been done to understand this allosteric mechanism. The results revealed interesting changes in the domain-domain coupling and multistate …
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Structural and functional investigations of mechanisms of iron-utilizing enzymes
… chemistry. Here, I discuss efforts to study the allosteric mechanisms of an essential human iron and free radical utilizing enzyme: ribonucleotide reductase (RNR), and efforts to elucidate the radical based mechanism of isonitrile formation by an mononuclear nonheme iron(II) α-ketoglutarate …
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Adenosine triphosphate is an allosteric inhibitor of coxsackievirus B3 3Dpol
… dynamics of the protein that are sensitive to allosteric effects of various mutations have been shown to be important determinants of fidelity. The research presented in this thesis provides the first direct evidence of allosteric regulation of 3Dpol by a small molecule. Inhibition assays …
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Towards structure and dynamics of metabolic networks
… is used to study the stabilizing effects of allosteric regulation in a model of human erythrocytes. Furthermore, the reactions of that model can be ranked according to their impact on stability of the steady state. The most important reactions in that respect are identified as hexokinase, …
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Structural and Functional Characterization of B. Anthracis Udp-Glcnac 2-Epimerase and Salmonella Secreted Effector I
… to 1.70 Å, explaining the mechanism of its allosteric regulation, as well as showing the first example of direct contact between an allosteric and catalytic substrate molecule. Arg210 was identified as a critical residue for both binding sites. Furthermore, the structure was used to design …
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Design and Synthesis of Inhibitors of Mycobacterium tuberculosis Menaquinone D (Mtb MenD) as Potential Therapeutics for Tuberculosis (Tb)
… to bind to a previously unreported allosteric regulation site on MenD, which was identified by our collaborators during the period of this work. Based on these findings, subsequent inhibitor series were designed with the aid of in silico docking and enumeration tools, with the aim of …
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