Digital Commons Network^™

The Distinctive Regulatory Mechanisms Of Bacterial Acetyl-Coa Carboxylase, Alexandra Leigh Evans

LSU Doctoral Dissertations

Metabolic Regulation is a complex system used to control cellular metabolism in response to conditions in the cell’s environment. For most enzymes, the cell can rely upon a minimal amount of regulation; however, critical enzymes, such as acetyl-CoA carboxylase, must be regulated at multiple levels. Acetyl-CoA carboxylase catalyzes the first committed step in fatty acid synthesis. In bacteria, acetyl-CoA carboxylase forms a complex of three subunits–biotin carboxylase, biotin carboxyl carrier protein, and carboxyltransferase–which catalyze the carboxylation of acetyl-CoA to form malonyl-CoA via two half-reactions. In the first half-reaction, biotin covalently linked to biotin carboxyl carrier protein is carboxylated by biotin …

Direct Quantification Of Deubiquitinating Enzyme Activity In Single Intact Cells, Nora Safabakhsh

LSU Doctoral Dissertations

Challenges in drug efficacy occur during the treatment of most types of cancer due to the heterogeneity of the tumor microenvironment. This has led to the development of personalized medicine. Due to the clinical success of the proteasome inhibitors Bortezomib and Carfilzomib in treatment of multiple myeloma, interest has shifted towards molecularly-targeted chemotherapeutics for ubiquitin-proteasome system (UPS). Deubiquitinating enzymes (DUBs) are an essential part of this pathway which have been found to promote Bortezomib resistance in multiple myeloma patients. Unfortunately, there is a lack of specific, high throughput biochemical assays to characterize DUB activity in patient samples before and after …

Exploring The Role Of Rna Polymerase Iii Complex Assembly On Ribosomal Dna Silencing In Saccharomyces Cerevisiae, Kyle Thomas Kern

LSU Doctoral Dissertations

The yeast rDNA region is host to a number of transcriptional regulatory elements, which work in conjunction to generate essential RNA subunits of ribosomes, as well as protecting the region from DNA damage. The role of RNA polymerase III complex binding at the 5S gene on rDNA silencing in the NTS2 region was investigated, both by use of a TY1:MET15 reporter insert and a MET15 gene integration at an endogenous SphI site. It was discovered that Pol III complexes do have an effect on reporter expression in the NTS2 region, though the specific effect was different based on the method …

Data-Driven Computational Approach To Study Bio-Molecular Interactions, Misagh Naderi

LSU Doctoral Dissertations

Proteins commonly convey their functions in coordination with other proteins, small molecules and/or other biological assemblies such as sugars, lipids, DNA or RNA. Understanding the nature of these interactions is therefore central to improving our knowledge of biological systems. This body of work is a consolidation of three different computational approaches to study bio-molecular interactions: large-scale protein-ligand modeling, fragment-based cheminformatics, and computational analysis of interactions in single proteins.

The first issue that is addressed in this study is the scarcity of atomic crystal structures of protein-drug complexes. In general, a drug molecule’s affinity for multiple protein targets may causes unsolicited …

Breaking Conventions: Ohrr, A Transcriptional Regulator From Burkholderia Thailandensis, Anuja Rajiv Pande

LSU Doctoral Dissertations

Organic peroxides (OPs) are highly toxic oxidants. They directly react with cellular macromolecules rendering them inactive. Soil bacteria live in an oxidative environment rich in OPs from plant exudates and other xenobiotic compounds. Bacteria also face a burst of organic peroxides (lipid peroxides) in the macrophages during host invasion. Prokaryotes sense oxidative changes in environment and modulate their gene expression as an adaptive response for survival. MarR (multiple antibiotic resistance regulators) proteins enable bacteria to respond to such stress. Resistance to organic oxidants has been hypothesized to help bacteria survive in presence of disinfectants. This increases nosocomial infection rate.

Bacteria …

Changes In Carbon, Nutrient, And Trace Metal Concentrations During The Transition From Freshwater To Marine Environments - A Case Study In Southwest Louisiana, Songjie He

LSU Doctoral Dissertations

Rivers carry terrestrial nutrients and other materials to estuaries, affecting biogeochemical cycles and ecosystems in coastal margins. This dissertation research incorporated five studies to investigate the dynamics of carbon, nutrients, and trace metals in four major coastal rivers in southwest Louisiana – the Sabine, Calcasieu, Mermentau, and Vermilion Rivers. The overarching goal of this research was to broaden the knowledge and understanding of biogeochemical processes in freshwater – saltwater mixing zones. These studies employed decade-long monitoring records of water chemistry, utilized monthly field measurements conducted over a two-year period, and used analysis of over 200 water samples for carbon, nitrogen, …

5-Lipoxygenase (5-Lox)-5-Lipoxygenase Activating Protein (Flap)-Nanodisc Complex: A Model For The 5-Lox-Flap Interaction, Erin Elizabeth Schexnaydre

LSU Doctoral Dissertations

Leukotrienes (LT) are lipid mediators of the inflammatory response that play important roles in diseases such as asthma and atherosclerosis. Leukotriene A4 (LTA₄) is synthesized from arachidonic acid (AA) by 5-lipoxygenase (5-LOX) with the help of 5-lipoxygenase activating protein (FLAP), a trimeric nuclear transmembrane protein. Exactly how 5-LOX and FLAP interact is not well understood, however FLAP is essential for the production of leukotrienes in vivo. I used nanodiscs (NDs), engineered membrane systems, as a tool to study the 5-LOX-FLAP interaction. FLAP was incorporated into NDs with a phospholipid composition to mimic of the nuclear membrane. Structural features …