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Biochemistry, Biophysics, and Structural Biology Commons™
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- Acetate metabolism (2)
- Cryptococcus neoformans (2)
- Trypanosoma brucei (2)
- ARF inhibitor (1)
- Acanthamoeba (1)
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- Allosteric enzyme (1)
- Balamuthia mandrillaris (1)
- Biochemistry (1)
- Carboxylcytosine (caC) (1)
- DNA glycosylase (1)
- DNA repair (1)
- Demethylation (1)
- Drug development (1)
- Enolase (1)
- Entamoeba histolytica (1)
- Enzyme kinetics (1)
- Enzymology (1)
- Epigenetics (1)
- Fatty acid uptake (1)
- Fatty acid uptake inhibitor (1)
- Fatty acids (1)
- Formylcytosine (fC) (1)
- Gap junction (1)
- Genetics (1)
- Glucokinase (1)
- Glucose (1)
- Grassofermata (1)
- Homologous Recombination (1)
- Innate immunity (1)
- Innexins (1)
Articles 1 - 18 of 18
Full-Text Articles in Biochemistry, Biophysics, and Structural Biology
Biochemical Analyses Of Udgx-A Crosslinking Uracil-Dna Glycosylase, Chuan Liang
Biochemical Analyses Of Udgx-A Crosslinking Uracil-Dna Glycosylase, Chuan Liang
All Dissertations
DNA base damage is common due to exposure to various endogenous and exogenous factors. To repair the base lesions, such as uracil from cytosine deamination, enzymes from the uracil-DNA glycosylase (UDG) superfamily are critical, which can recognize the damaged base and initiate the base excision repair (BER) pathway. There used to be six families of proteins identified in the UDG superfamily until a new member, UDGX, was found in Mycobacterium smegmatis, which is a unique DNA-crosslinking UDG. In this dissertation work, a series of biochemical analyses of the newly found UDGX are performed, including the analyses of structures, functions, …
Characterization Of The Effects Of The Pyrazolopyrimidine Inhibitor Grassofermata (Nav-2729) In The Eukaryotic Pathogen Trypanosoma Brucei, Kristina Marie Parman
Characterization Of The Effects Of The Pyrazolopyrimidine Inhibitor Grassofermata (Nav-2729) In The Eukaryotic Pathogen Trypanosoma Brucei, Kristina Marie Parman
All Dissertations
The protozoan pathogen, Trypanosoma brucei, is the causative agent of sleeping sickness in humans and nagana in livestock in sub-Saharan Africa. T. brucei cycles between tsetse fly and mammalian hosts, and it is adapted to survive in diverse host tissues. Variant Surface Glycoprotein (VSG) plays a key role in immune evasion in the mammalian host. The VSG membrane anchor requires two myristates, 14-carbon saturated fatty acids (FAs) that are scarce in the host. T. brucei can synthesize FAs de novo, but also readily takes up exogenous FAs, despite lacking homologs to fatty acid uptake proteins found in other …
Biochemical And Kinetic Analysis Of Phosphofructokinase In The Eukaryotic Human Pathogen Entamoeba Histolytica, Jin Cho
All Dissertations
Entamoeba histolytica is a water- and food-borne intestinal parasite that causes amoebiasis and liver abscess in ~100 million people each year leading to ~100,000 deaths. This amitochondriate parasite lacks many metabolic pathways including the tricarboxylic acid cycle and oxidative phosphorylation, and cannot synthesize purines, pyrimidines, or most amino acids. As a result, E. histolytica is presumed to rely on its modified pyrophosphate (PPi)-dependent glycolytic pathway for ATP production during growth on glucose. This pathway relies on a PPi-dependent rather than ATP-dependent phosphofructokinase (PFK) and thus has a net production of three ATP per glucose. However, in …
Elucidating Acetate Metabolism: Identification Of Transporters And Enzymes Required For Acetate Utilization In The Fungal Pathogen Cryptococcus Neoformans, Perry L. Kezh
All Dissertations
Cryptococcus neoformans is the leading cause of fungal meningitis world-wide. While exposure to this environmental sporophyte is common during childhood, those who are immune compromised are at risk of infection. Following inhalation, this basidiomycetous fungus subsequently colonizes other organs though hematogenous dissemination, eventually crossing the blood brain barrier and colonizing the brain where it causes as cryptococcal meningitis. Changes in the availability of carbon sources stemming from the movement from soil to the lungs induce changes in fungal metabolism. Specifically, alveolar macrophages, which present a first line of defense against infection, provide a glucose-/amino acid-poor environment. As such, the use …
Fatty Acids And Parasitism: Towards A Better Understanding Of Lipid Metabolism In Trypanosoma Brucei, Joshua Saliutama
Fatty Acids And Parasitism: Towards A Better Understanding Of Lipid Metabolism In Trypanosoma Brucei, Joshua Saliutama
All Dissertations
Trypanosoma brucei is an extracellular eukaryotic parasite that causes sleeping sickness in humans and cattle. As an extracellular parasite, T. brucei relies on the host’s nutrients to satisfy its growth requirements. The parasite is unusual because it does not uptake most of the host’s lipid species. Instead, T. brucei prefers to perform de novo synthesis of most lipid species. One of the lipid species that T. brucei can both uptake and synthesize is fatty acids. In my thesis work, I investigated the dynamics of fatty acid uptake, metabolism, and utilization of T. brucei. My work starts by determining the …
Biochemical Characterization Of Ssb1, Ssb2, Sycp3, And Meilb2 In Meiotic Recombination, Garrett Buzzard
Biochemical Characterization Of Ssb1, Ssb2, Sycp3, And Meilb2 In Meiotic Recombination, Garrett Buzzard
All Dissertations
The genome is constantly at risk to damage from environmental and normal cellular processes. Double-strand breaks (DSBs) are one of the most deleterious forms of DNA damage as unrepaired DSBs ultimately result in cell death. Homologous recombination (HR) is a conserved DNA repair pathway that utilizes a homologous chromosome as a template for DNA synthesis to repair the DSBs relatively error-free. HR is active in both mitotic and meiotic cells but meiotic HR is initiated by the introduction of programmed DSBs into the genome. The process of HR repairs the DSBs and results in a physical connection between homologous chromosomes …
Functional Analysis Of Two Campoletis Sonorensis Ichnovirus Vinnexins In Drosophila Melanogaster, Peng Zhang
Functional Analysis Of Two Campoletis Sonorensis Ichnovirus Vinnexins In Drosophila Melanogaster, Peng Zhang
All Dissertations
Campoletis sonorensis Ichnovirus (CsIV) is produced by the ichneumonid parasitoid Campoletis sonorensis (the primary host). Female parasitoid wasps restrictedly replicate viruses in their ovaries and inject them into a larval lepidopteran (secondary host) during oviposition. This symbiotic virus of C. sonorensis is essential for successful parasitization. CsIV is characterized by having a large, segmented double-stranded DNA genome with a large number of genes, many of which are associated with one of five multigene families. The CsIV vinnexin gene family is one of them and has four members, including CsIV-vnxD and CsIV-vnxG. Vinnexins are homologues of insect Innexins, which form gap …
Methyltransferase, Glucose Adaptation, And Import Complex In Trypanosoma Brucei, Emily Knight
Methyltransferase, Glucose Adaptation, And Import Complex In Trypanosoma Brucei, Emily Knight
All Dissertations
Trypanosoma brucei is a kinetoplastid parasite responsible for human African trypanosomiasis (HAT) and nagana, a livestock wasting disease, which both endemic to sub-Saharan Africa. Unique to kinetoplastids are the specialized peroxisomes, named glycosomes, which compartmentalize the first several steps of glycolysis and gluconeogenesis, nucleotide sugar biosynthesis, and many other metabolic processes. Kinetoplastids are unique in that they have a single mitochondrion. In this work, I present the first study into SET domain proteins in any kinetoplastid parasites. We have characterized a predicted SET domain protein, TbSETD3, that localizes to the mitochondrion and a depletion of the protein results in growth …
New Dna Repair And Demethylation Functions In Uracil Dna Glycosylase Superfamily, Chenyan Chang
New Dna Repair And Demethylation Functions In Uracil Dna Glycosylase Superfamily, Chenyan Chang
All Dissertations
Uracil-DNA glycosylase (UDG) superfamily, which consists of several groups of enzymes that recognize the damaged DNA bases and initiate the base excision repair (BER) pathway, is most important in dealing with DNA deamination and other base modifications. Thymine DNA glycosylase (TDG), which belongs to family 2 in the UDG superfamily, is able to specifically recognize and cleave the 5-methylcytosine (mC) oxidative derivatives including 5-formylcytosine (fC), 5-carboxylcytosine (caC), 5-hydromethyluracil (hmU) caused by active demethylation or DNA damage. My dissertation work is mainly focused on the fC and caC glycosylase activity within UDG superfamily. Chapter 1 is a general introduction to the …
Glycolytic Inhibitors As Leads For Drug Discovery In The Pathogenic Free-Living Amoebae, Jillian Milanes
Glycolytic Inhibitors As Leads For Drug Discovery In The Pathogenic Free-Living Amoebae, Jillian Milanes
All Dissertations
The free-living amoeba, Naegleria fowleri, can cause a rare yet usually lethal infection of the brain called primary amebic meningoencephalitis. Because of poor diagnostics and limited treatment options, the mortality rate associated with the disease is >97%. Due to our finding that glucose is critical for trophozoite growth in culture, we have been interested in exploiting amoebae glucose metabolism to identify new potential drug targets. We have characterized the first enzyme of the glycolytic pathway, glucokinase (Glck), from N. fowleri and two other pathogenic free-living amoeba, Acanthamoeba castellanii and Balamuthia mandrillaris. We have assessed their biochemical properties and …
Comparing Development Of Drug Resistance By Cryptococcus Neoformans To Chemically Distinct Azole Anti-Fungal Compounds, Lindsey Burke
Comparing Development Of Drug Resistance By Cryptococcus Neoformans To Chemically Distinct Azole Anti-Fungal Compounds, Lindsey Burke
Honors College Theses
Cryptococcus neoformans is a fungus that primarily infects humans who have weakened immune systems. An azole drug, Fluconazole, is commonly administered against C. neoformans in regions were cryptococcosis is most prevalent, most notably Sub-Saharan Africa. However, C. neoformans can gain resistance to Fluconazole through becoming an aneuploid. To better understand the basis of resistance, we employed a disk diffusion assay and investigated several chemically-distinct azole compounds with anticryptococcal properties for their effectiveness against C. neoformans and to identify potential differences in the capacity of the fungus to become resistant to each of the tested compounds. Different C. neoformans strains were …
Function Of Septin Proteins In Cryptococcus Neoformans In Cell Wall And Plasma Membrane Integrity And Homeostasis, Emma Hatchell
Function Of Septin Proteins In Cryptococcus Neoformans In Cell Wall And Plasma Membrane Integrity And Homeostasis, Emma Hatchell
Honors College Theses
Cryptococcus neoformans is a pathogenic basidiomycetous yeast that causes meningitis in immunocompromised patients. This lethal fungus is sometimes referred to as the “sugar coated killer” due to its polysaccharide capsule. It is estimated that 152,000 cases of cryptococcal infection occur each year and result in 112,000 deaths. The ability of C. neoformans to adapt to host temperature is a main factor responsible for virulence. Septins are conserved filament-forming GTPases that are confirmed to be involved in cytokinesis and morphogenesis and have been implicated in heat stress response and virulence of C. neoformans. C. neoformans genome encodes four septins, Cdc3, …
Biochemical Analysis Of Dna Glycosylase In Dragonfish (Scleropages Formosus, Sfo) Tdg, Jenna Perry
Biochemical Analysis Of Dna Glycosylase In Dragonfish (Scleropages Formosus, Sfo) Tdg, Jenna Perry
Honors College Theses
TDG, which is a member of the uracil DNA glycosylase superfamily, plays a critical role in the active demethylation process in mammals by removing oxidized derivatives of 5-methylcytosine (mC). While human TDG has been extensively studied and found to possess 5-formylcytosine and 5-carboxylcytosine DNA glycosylase activity, little is known regarding this demethylation process in vertebrates other than the human species. Previous research proposed a catalytic sequence in motif 1 of zebrafish TDG1 and TDG2 that modulates DNA glycosylase activity based on mutational, kinetic, and modeling analyses of these enzymes. Building on this work, researchers discovered that the Sfo TDG is …
The Role Of Fto, A Human Rna Demethylase In Perennial Grass Development And Abiotic Stress Responses, Andrew Fiorentino, Qian Hu, Xiaotong Chen, Zhaohui Chen
The Role Of Fto, A Human Rna Demethylase In Perennial Grass Development And Abiotic Stress Responses, Andrew Fiorentino, Qian Hu, Xiaotong Chen, Zhaohui Chen
Honors College Theses
The integration of the human fat mass and obesity associated (FTO) gene into turfgrass is a novel approach at improving cell proliferation and abiotic stress resistance. The FTO protein is an RNA demethylase responsible for epigenetic regulation of the genome. In related rice, the gene is associated with increased crop yield, tiller number, and aerial biomass. It is proposed to work via demethylation of repeat RNA associated with chromatin remodeling, causing widespread transcriptional activation. In this study, the feasibility of using FTO for plant trait modification in perennial grasses is being investigated. Potentially transformed embryogenic calli of creeping bentgrass with …
Investigating The Role Of Cnag_05113 In The Carnitine Biosynthesis Pathway In Cryptococcus Neoformans., Jasmine Meltzer, Rodrigo Catalan-Hurtado, Perry Kezh, Kerry Smith
Investigating The Role Of Cnag_05113 In The Carnitine Biosynthesis Pathway In Cryptococcus Neoformans., Jasmine Meltzer, Rodrigo Catalan-Hurtado, Perry Kezh, Kerry Smith
Honors College Theses
Cryptococcus neoformans, the leading cause of fungal meningitis, is a fungal pathogen that causes severe infection of the central nervous system in patients with compromised immune systems, typically caused by HIV/AIDS. C. neoformans infections are present in developed countries including the United States, but most fatalities occur in sub-Saharan Africa where antiretroviral therapy, the treatment for HIV/AIDS, is less accessible. Current treatments for severe cryptococcal infections are extensive and outdated. There is a critical need for an improved understanding of the fungus and new targeted therapies. Our goal is to identify metabolic pathways important to the survival of C. …
Acetate Metabolism In The Fungal Pathogen Cryptococcus Neoformans, Oly Ahmed
Acetate Metabolism In The Fungal Pathogen Cryptococcus Neoformans, Oly Ahmed
All Dissertations
Cryptococcus neoformans is an environmental basidiomycetous fungus with a worldwide distribution and a wide range of habitats. Inhalation of the desiccated yeasts or spores of C. neoformans often leads to opportunistic pulmonary infections in immunocompromised individuals, and in severe cases causes lethal meningitis following hematogenous dissemination. During infection, depending on the tissue and disease state, the invading fungi experience a range of nutrient microenvironments within the host body. As a result, rapid metabolic adaptations geared towards efficient utilization of carbon sources alternative to glucose become one of the prime determinants of survival and growth for the pathogen. Incidentally, cryptococcal infection …
Inhibitors Of Human Eno2 Are Potent Anti-Trypanosomal Agents, Danielle Lavigne
Inhibitors Of Human Eno2 Are Potent Anti-Trypanosomal Agents, Danielle Lavigne
Honors College Theses
Kinetoplastid parasite infections remain a global health burden. Here, we have characterized inhibitors of an essential Trypanosoma brucei glycolytic enzyme, enolase (TbENO). We anticipate TbENO inhibitors will be potent anti-trypanosomals, as T. brucei relies on glycolysis for ATP production in the blood of infected mammals. Additionally, the phosphonate enolase inhibitors being considered are well-tolerated in mammals, suggesting their potential in developing novel therapeutics for kinetoplastid infections. TbENO was cloned into the bacterial expression vector, pQE-30, and the heterologously-expressed protein was purified by nickel affinity and assayed in a coupled enzyme assay. Enzyme activity paralleled the abundance …
Attenuation Of Human Dmc1 Recombination Activities By Substitution Of A Conserved Residue, Melody Hayman
Attenuation Of Human Dmc1 Recombination Activities By Substitution Of A Conserved Residue, Melody Hayman
All Theses
Unrepaired DNA double strand breaks (DSB) are detrimental to the viability of the cell. The repair of DSBs can occur by a process called homologous recombination (HR). HR is used whenever the cell has a homologous template in the way of a homologous chromosome available. The process of HR during mitosis is different from meiotic HR. To initiate meiotic recombination, DSBs are formed and processed to allow proper chromosome segregation and ultimately genetic variation. Meiotic HR is mediated by the meiosis specific recombinase, DMC1. The DMC1 recombinase binds to the 3’ end of a newly resected DSB forming a nucleoprotein …