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Full-Text Articles in Biochemistry, Biophysics, and Structural Biology

Vitamin D Metabolites And Their Intestinal Responses, Carmen J. Reynolds Jan 2019

Vitamin D Metabolites And Their Intestinal Responses, Carmen J. Reynolds

Graduate Theses and Dissertations

Vitamin D metabolites regulate calcium absorption in the intestines through activation of the vitamin D receptor (VDR) and resulting in increased expression of calcium-associated proteins. Presently, it is thought that vitamin D metabolizes into a hormonal form, 1,25-dihydroxyvitamin D (1,25D), and the hormone then circulates via blood to the duodenum to stimulate calcium absorption. Recently, Koszewski et al. proposed that delivery of the hormone occurs via digestive passage rather than by the blood (Koszewski et al., 2012). Growing evidence has suggested, instead, that the hormonal precursor, 25-hydroxyvitamin D (25D), may have functional activity by either providing substrate for ...


Fatty Acid Amides And Their Biosynthetic Enzymes Found In Insect Model Systems, Ryan L. Anderson Nov 2018

Fatty Acid Amides And Their Biosynthetic Enzymes Found In Insect Model Systems, Ryan L. Anderson

Graduate Theses and Dissertations

A fatty acid amide is precisely as the name suggests: A fatty acid (CHn-COOH), in which the hydroxyl group of the carboxylic acid is displaced by an amine functional group from a biogenic amine (R-NH2), ultimately forming an amide bond. Furthermore, these fatty acid amides can be composed of a variety of different acyl chain lengths donated by the fatty acid and a myriad of different biogenic amines. Thus, these molecules can be subdivided in a number of different ways including the separation of short chain (acetyl to heptanoyl) and long chain (palmitoyl to arachidonoyl) and also based off the ...


Investigating The Roles Of Fucosylation And Calcium Signaling In Melanoma Invasion, Tyler S. Keeley Nov 2018

Investigating The Roles Of Fucosylation And Calcium Signaling In Melanoma Invasion, Tyler S. Keeley

Graduate Theses and Dissertations

Melanoma is the deadliest form of skin cancer. Prognosis for early stage melanoma patients is excellent, and surgery is often curative for these patients. However, once patients have presented with invasive disease, the average 5-year survival rate drops significantly from over 90% to between 10 and 15%. Several therapies have been developed to target a commonly mutated oncogene BRAF, or its downstream effectors. Unfortunately, while these treatments show robust initial response, most patients relapse within a year. Moreover, therapy-resistant tumors are often more invasive and metastatic. Therefore, it is important to investigate the molecular mechanisms underlying melanoma invasion and metastasis ...


Investigating The Role Of The Rna Binding Protein Lin28 In The Human Placenta: Implications For Preeclampsia, John Canfield Nov 2018

Investigating The Role Of The Rna Binding Protein Lin28 In The Human Placenta: Implications For Preeclampsia, John Canfield

Graduate Theses and Dissertations

An essential event during early pregnancy is the invasion of trophoblasts into the maternal decidua, which is necessary for proper implantation and establishment of maternal-fetal interface and ultimately allows for proper nutrient exchange and immunological tolerance of the growing fetus. For this invasion to occur, cells originating from the trophectoderm undergo an epithelial to mesenchymal transition to become invasive extravillous trophoblasts and begin invading the uterine decidual tissue. Through the secretion of matrix metalloproteinases and through interactions with many cytokines and cell-adhesion molecules, this well-orchestrated process of trophoblast invasion results in extensive remodeling of the maternal spiral vasculature by the ...


The Role Of Phosphohistidine Phosphatase 1 In Ethanol-Induced Liver Injury, Daniel Richard Martin Apr 2018

The Role Of Phosphohistidine Phosphatase 1 In Ethanol-Induced Liver Injury, Daniel Richard Martin

Graduate Theses and Dissertations

Chronic liver diseases, which includes alcoholic liver disease (ALD), are consistently among the top 15 leading causes of death in the United States. ALD is characterized by progression from a normal liver to fatty liver disease (hepatic steatosis), which can lead to cirrhosis, alcoholic hepatitis, and liver failure. We have identified a novel role of phosphohistidine signaling, mediated through phosphohistidine phosphatase 1 (PHPT1), in the onset of hepatic steatosis. We have identified PHPT1 as a target of selective oxidation following acute ethanol exposure as well as being downregulated following chronic ethanol exposure. We mapped the oxidative modification site and developed ...


Investigation Of Alcohol-Induced Changes In Hepatic Histone Modifications Using Mass Spectrometry Based Proteomics, Crystina Leah Kriss Apr 2018

Investigation Of Alcohol-Induced Changes In Hepatic Histone Modifications Using Mass Spectrometry Based Proteomics, Crystina Leah Kriss

Graduate Theses and Dissertations

Alcohol liver disease (ALD) is a major health concern throughout the world. Currently, in the United States, 17 million people suffer from alcoholism, of which 1.4 million people are receiving treatment [1, 2]. The link between ethanol metabolism, reactive oxygen species (ROS) and liver injury in ALD has been well characterized over the last couple decades [3-10]. Ethanol metabolism relies on the availability of the cofactor NAD+ for the oxidation of ethanol into acetate, consequently causing alterations in redox potential. Redox dysfunction within the mitochondria can affect multiple pathways important in maintaining cellular homeostasis. Chapter 1 provides an introduction ...


Elastin-Like Polypeptide Fusion Tag As A Protein-Dependent Solubility Enhancer Of Cysteine-Knot Growth Factors, Tamina L. Johnson Apr 2018

Elastin-Like Polypeptide Fusion Tag As A Protein-Dependent Solubility Enhancer Of Cysteine-Knot Growth Factors, Tamina L. Johnson

Graduate Theses and Dissertations

Elastin-like peptide (ELP) fusions promote therapeutic delivery and efficacy. Recombinant proteins, like neurotrophins, lack bioavailability, have short in vivo half-lives, and require high manufacturing costs. Fusing recombinant proteins with genetically encodable ELPs will increase bioavailability, enhance in vivo solubilization, as well as provide a cost-effective method for purification without the need for chromatography. During expression of neurotrophin-ELP (N-ELP) fusions, dense water-insoluble aggregates known as inclusion bodies (IBs) are formed. Inclusion bodies are partially and misfolded proteins that usually require denaturants like Urea for solubilization. Strong denaturants arrest ELPs stimuli-responsive property and increase unwanted aggregation, making purification difficult, yet possible. The ...


Analyzing The Effects Of Ca2+ Dynamics On Mitochondrial Function In Health And Disease, Patrick Toglia Apr 2018

Analyzing The Effects Of Ca2+ Dynamics On Mitochondrial Function In Health And Disease, Patrick Toglia

Graduate Theses and Dissertations

Mitochondria plays a crucial role in cells by maintaining energy metabolism and directing cell death mechanisms by buffering calcium (Ca2+ )from cytosol. Therefore, the Ca2+ overload of mitochondria due to the upregulated cytosolic Ca2+ , observed in many neurological disorders is hypothesized to be a key pathway leading to mitochondrial dysfunction and cell death. In particular, Ca2+ homeostasis disruptions due to Alzheimer’ s disease (AD)-causing presenilins (PS1/PS2) and oligomeric forms of β-amyloid peptides Aβ commonly found in AD patients are presumed to cause detrimental effects on the mitochondria and its ability to function properly. We ...


Design, Synthesis, Application Of Biodegradable Polymers, Mussie Gide Mar 2018

Design, Synthesis, Application Of Biodegradable Polymers, Mussie Gide

Graduate Theses and Dissertations

Bacterial infections have posed a serious threat to the public health due to the significant rise of the infections caused by antibiotic-resistant bacteria. There has been considerable interest in the development of antimicrobial agents which mimic the natural HDPs, and among them biodegradable polymers are newly discovered drug candidates with ease of synthesis and low manufacture cost compared to synthetic host defense peptides. Herein, we present the synthesis of biocompatible and biodegradable polymers including polycarbonate polymers, unimolecular micelle hyperbranched polymers and dendrimers that mimic the antibacterial mechanism of HDPs by compromising bacterial cell membranes. The developed amphiphilic polycarbonates are highly ...


Exploring Rna Interference In The Agricultural Pests Western Corn Rootworm, Fall Armyworm, And Southern Green Stink Bug, Courtney Anne Davis-Vogel Jan 2018

Exploring Rna Interference In The Agricultural Pests Western Corn Rootworm, Fall Armyworm, And Southern Green Stink Bug, Courtney Anne Davis-Vogel

Graduate Theses and Dissertations

RNA interference (RNAi) is a highly conserved cellular process whereby small regulatory RNAs bound to argonaute proteins produce sequence-specific silencing of longer complementary RNAs. The agricultural biotechnology industry has taken advantage of RNAi to control insect pests through the use of transgenic crops expressing insecticidal RNAs. Upon introduction of double-stranded RNA into a pest, the complementary target messenger RNA is depleted and results in a lethal phenotype. For reasons that are not fully defined, certain insects respond differently to orally introduced RNAs, leaving holes in the manageability of all agricultural pests through this promising new technology. Furthermore, there are indications ...


Elucidating How N-Glycosylation Impacts Immunoglobulin G Fc Structure And Receptor Binding, Daniel Falconer Jan 2018

Elucidating How N-Glycosylation Impacts Immunoglobulin G Fc Structure And Receptor Binding, Daniel Falconer

Graduate Theses and Dissertations

N-linked glycans are post-translational modifications that link an oligosaccharide to an asparagine residue. The attached oligosaccharide then undergoes extensive modification in the Golgi apparatus prior to protein secretion. This type of modification helps with protein folding, resistance to protease activity, immunogenicity, and imparting biological activity. Antibodies, such as IgG1, offer an idealized system to study proteins containing an N-linked glycan.

IgG1 is a homodimeric protein with a molecular weight of 150 kDa. It is composed of two heavy and two light chains, the heavy chain encompassing the Fab (fragment antigen binding) and Fc (fragment constant) and the light chain only ...


Effects Of Flanking Dna And A Transcriptional Activator On The Histone Acetyltransferase Activity Of The Saga Complex, Sannie J. Culbertson Jan 2018

Effects Of Flanking Dna And A Transcriptional Activator On The Histone Acetyltransferase Activity Of The Saga Complex, Sannie J. Culbertson

Graduate Theses and Dissertations

Though many of the proteins and protein complexes involved in eukaryotic gene expression have been identified, mechanistic knowledge about how the proteins interact with and influence one another to promote gene expression remains limited. In this work, we have started to tease out the effects of an activator protein and the chromatin environment on the HAT activity of the SAGA complex. In contrast to the prevailing model of stimulation in which activator was believed to increase the binding affinity of SAGA for chromatin, we observed that activator increases the turnover rate of acetylation by SAGA on chromatin substrates. We have ...


Characterization Of A Mucopolysaccharidosis Type I And Galnac Transferase Deficiency Double Knockout Mouse, Karan Gera Jan 2018

Characterization Of A Mucopolysaccharidosis Type I And Galnac Transferase Deficiency Double Knockout Mouse, Karan Gera

Graduate Theses and Dissertations

The mucopolysaccharidoses (MPSs) are a group of lysosomal storage diseases (LSDs) which are characterized by the aberrant primary storage of glycosaminoglycans (GAGs) in lysosomes of multiple organ and tissue systems. The most commonly diagnosed is MPS Type I (MPS I), caused by mutations in the gene which codes for α-L-iduronidase (IDUA). Biochemically, MPS I is characterized by the aberrant primary lysosomal storage of incompletely degraded dermatan and heparan sulfates, along with a secondary accumulation of gangliosides and other compounds in lysosomes. Its clinical manifestation in severe form leads to early death, characterized by progressive central nervous system disease (with behavioral ...


Using Genomic And Gene Expression Methods To Understand The Phenotypic Response Of Soybean To Sudden Death Syndrome Caused By Fusarium Virguliforme, Alexander Stephen Luckew Jan 2018

Using Genomic And Gene Expression Methods To Understand The Phenotypic Response Of Soybean To Sudden Death Syndrome Caused By Fusarium Virguliforme, Alexander Stephen Luckew

Graduate Theses and Dissertations

Soybean sudden death syndrome (SDS) is one of the most important soybean diseases in the Midwestern United States, leading to average losses of $396 million per year from 1996 to 2015. The causal agent of SDS, soilborne fungus Fusarium virguliforme (Fv), causes root rot symptoms and releases phytotoxins taken up by the plant to produce chlorosis and necrosis in the leaves. The main management practice used to reduce the impact of SDS is planting resistant soybean cultivars. Resistance to SDS is known to be quantitative with 88 known quantitative trait loci (QTL) based on Soybase.org. Many of these QTL ...


Effect Of Increased Ratio Of Butyrate To Physiological Concentrations Of Acetate And Propionate On Intestinal Integrity And Il-8 Secretion In Caco-2 Cells, Nidhi Shah Jan 2018

Effect Of Increased Ratio Of Butyrate To Physiological Concentrations Of Acetate And Propionate On Intestinal Integrity And Il-8 Secretion In Caco-2 Cells, Nidhi Shah

Graduate Theses and Dissertations

Background: Inflammatory bowel diseases (IBD) are a growing global health problem. Current pharmacological therapies are not effective in all IBD patients, tend to cause side effects and in some cases lose effectiveness when used for a prolonged period of time. Hence, there is a need to develop dietary interventions that are safe and be applicable to all. Chronic inflammation of the gut could be combated by increasing the consumption of dietary fiber which would lead to an increased butyrate production in the colon. Butyrate has been shown to improve intestinal integrity and suppress the secretion of pro-inflammatory cytokine, IL-8 – which ...


Point Mutational Examination Of Eukaryotic Initiation Factor 4e (Eif4e), Inclusion Bodies Analysis, And Barley Yellow Dwarf Virus (Bydv) Exonuclease Resistant Rna Structure Mapping And Prediction, Melissa Kathryn Sheber Jan 2018

Point Mutational Examination Of Eukaryotic Initiation Factor 4e (Eif4e), Inclusion Bodies Analysis, And Barley Yellow Dwarf Virus (Bydv) Exonuclease Resistant Rna Structure Mapping And Prediction, Melissa Kathryn Sheber

Graduate Theses and Dissertations

Eukaryotic initiation factor 4E (eIF4E) binds the 5’m7GTP cap structure of mRNA in order to facilitate effective translation. Recessive eIF4E alleles harboring naturally occurring point mutations have been associated with resistance to viral infection, particularly in members of the genus Potyvirus. Resistance is thought to be conferred by disrupting the binding of the 5’ viral-encoded protein (VPg), covalently attached to the 5’ end of the Potyvirus genomic RNA, to eIF4E. RNAs of members of the genus Panicovirus, some Carmoviruses and one Umbravirus however, bind eIF4E through a 3’ cap independent translation element (3’CITE) termed the PTE (Panicum mosaic ...


Structure And Function Of Xyloglucan Xylosyltransferases, Alan Culbertson Jan 2018

Structure And Function Of Xyloglucan Xylosyltransferases, Alan Culbertson

Graduate Theses and Dissertations

The plant cell wall is a complex network composed mainly of polysaccharides, the most abundant biopolymers on earth and a rich source of biorenewable materials. Biosynthesis of these plant polysaccharides is poorly understood, largely due to difficulties in the structural characterization of glycosyltransferases and lack of suitable substrates for in vitro analysis. Xyloglucan Xylosyltransferases (XXTs) initiate side-chain extensions from a linear glucan polymer by transferring the xylosyl group from UDP-xylose during xyloglucan biosynthesis. Here, we optimized protein expression and enzymatic activity conditions of XXTs through numerous N- and C-terminal truncations, various E. coli strains, solubility tags, and storage conditions. This ...


Impact Of Acute Heat Treatment On Autophagy And Insulin Signaling In C2c12 Myotubes, Corey Michael Summers Jan 2018

Impact Of Acute Heat Treatment On Autophagy And Insulin Signaling In C2c12 Myotubes, Corey Michael Summers

Graduate Theses and Dissertations

A major risk factor for the development of type 2 diabetes is reduced skeletal muscle insulin sensitivity. It is known that exercise and caloric restriction can improve skeletal muscle insulin resistance, but the mechanism by which this occurs is not completely elucidated. The AMP-activated protein kinase (AMPK), is thought to be a major contributor to the metabolic benefits observed after exercise training and caloric restriction. Activation of AMPK in skeletal muscle can have a wide range of effects, one of which is the initiation of macroautophagy (herein referred to as autophagy). Autophagy is the bulk degradation system of the cell ...


Molecular Mechanisms Governing Plant Parasitic Nematode Signaling And Host Parasitism, Stacey Nicola Barnes Jan 2018

Molecular Mechanisms Governing Plant Parasitic Nematode Signaling And Host Parasitism, Stacey Nicola Barnes

Graduate Theses and Dissertations

Pathogen infection of crops causes large-scale annual yield losses for farmers worldwide and hinders global efforts to provide adequate amounts of nutrition for the ever-growing human population. Plant-parasitic nematodes (PPN) are among some of the most devastating pathogens due to their ability to parasitize an expansive variety of agriculturally important crops. In order to identify ways to attenuate PPN infection and limit yield losses it is vital that we increase our understanding of host-PPN interactions. Here we investigate the molecular mechanisms that are occurring both within PPN and at the interface between PPN and their host plants.

Research into PPN-derived ...


Investigating The Interplay Of Physiological And Molecular Mechanisms Underpinning Programmable Aspects Of Heat Stress In Pigs, Jacob Seibert Jan 2018

Investigating The Interplay Of Physiological And Molecular Mechanisms Underpinning Programmable Aspects Of Heat Stress In Pigs, Jacob Seibert

Graduate Theses and Dissertations

Heat stress (HS) undermines production efficiency in all animal agriculture, culminating in major economic losses annually. The effects of HS in pigs is realized through depressed growth, altered body composition, and impaired reproductive performance. Pigs, unlike other mammals, do not possess functional sweat glands, making them rely on other mechanisms to thermoregulate during a heat challenge. Continual investigation of hyperthermia in pigs is crucial for developing new strategies and/or technologies that mitigate the effects of HS imposed on the pork industry. The studies conducted in this dissertation investigate the complex interplay of whole-animal physiology as well as cellular and ...


Dielectrophoresis At Wireless Bipolar Electrode Arrays: Applications To The Marker-Free Selection And Detection Of Circulating Tumor Cells, Min Li Jan 2018

Dielectrophoresis At Wireless Bipolar Electrode Arrays: Applications To The Marker-Free Selection And Detection Of Circulating Tumor Cells, Min Li

Graduate Theses and Dissertations

Metastasis is responsible for approximately 90% of cancer related deaths. The key step in metastasis is the migration of cancer cells out of the primary tumor and into bloodstream. Once reaching at a distant site, a fraction of these circulating tumor cells (CTCs) invades foreign tissues for subsequent growth of tumors. However, conventional cancer treatments ignore the metastatic process, resulting in cancer relapse. Consequently, the isolation and characterization of CTCs are crucial in understanding how cancer spread by metastasis.

The enormous value of CTCs has not been completely realized because isolation of CTCs – the first inevitable step of overall analysis ...


Comparison And Evaluation Of Two Rapid Diagnostic Assays For The Identification Of Mycoplasma Species, Aric James Mcdaniel Jan 2018

Comparison And Evaluation Of Two Rapid Diagnostic Assays For The Identification Of Mycoplasma Species, Aric James Mcdaniel

Graduate Theses and Dissertations

Members of the class Mollicutes are unique among bacteria in that they are unable to synthesize a cell wall. These organisms are also difficult to culture and very slow-growing with some species requiring up to 40 days to culture. Many of these bacteria are also significant pathogens in humans and animals, so rapid identification of isolates is a necessary diagnostic step. Many different tests are used for identification of pathogenic Mollicutes (primarily Mycoplasma and Ureaplasma species), however most tests are not cost or time efficient. Two relatively recent diagnostic tools are matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry and ...


Investigations Into The Non-Mevalonate Isoprenoid Biosynthesis Pathway's First Two Enzymes Utilizing Hybrid Qm/Mm Techniques, Justin K. White Nov 2017

Investigations Into The Non-Mevalonate Isoprenoid Biosynthesis Pathway's First Two Enzymes Utilizing Hybrid Qm/Mm Techniques, Justin K. White

Graduate Theses and Dissertations

Molecular drug design begins with the identication of a problem to solve. This work identies the growing resistance among human pathogens to current treatments. Once the problem is identied and understood, solutions must be proposed. This one is straight forward, we need new antimicrobial drugs. More specically, we need to identify novel targets to inhibit. A large portion of antibiotics focus on disruption of macromolecular production while only a few target metabolic systems. Finally, you need to propose solutions based on the information gathered. In order to avoid existing resistance, it is important to avoid the macromolecular route and focus ...


Role Of Heat Shock Transcription Factor 1 In Ovarian Cancer Epithelial-Mesenchymal Transition And Drug Sensitivity, Chase David Powell Nov 2017

Role Of Heat Shock Transcription Factor 1 In Ovarian Cancer Epithelial-Mesenchymal Transition And Drug Sensitivity, Chase David Powell

Graduate Theses and Dissertations

The heat shock response (HSR) is a robust cellular reaction to mitigate protein damage from heat and other challenges to the proteome. This protective molecular program in humans is controlled by heat shock transcription factor 1 (HSF1). Activation of HSF1 leads to the induction of an array of cytoprotective genes, many of which code for chaperones. These chaperones, known as heat shock proteins (HSPs), are responsible for maintaining the functional integrity of the proteome. HSPs achieve this by promoting proper folding and assembly of nascent proteins, refolding denatured proteins, and processing for degradation proteins and aggregates which cannot be returned ...


18f-Fdg Pet/Ctct-Based Radiomics For The Prediction Of Radiochemotherapy Treatment Outcomes Of Cervical Cancer, Badereldeen Abdulmajeed Altazi Nov 2017

18f-Fdg Pet/Ctct-Based Radiomics For The Prediction Of Radiochemotherapy Treatment Outcomes Of Cervical Cancer, Badereldeen Abdulmajeed Altazi

Graduate Theses and Dissertations

Cervical cancer remains the third most commonly diagnosed gynecological malignancy in the United States and throughout the world despite being potentially preventable. Patients diagnosed with cervical cancer may develop local recurrence in the cervix and surrounding structures (vaginal apex, parametrial, or paracervical), regional recurrence in pelvic lymph nodes, distant metastasis, or a combination of all. The management of such treatment outcomes has not been subject to rigorous investigation. Therefore, there is a need for studies and clinical trials that focus on decision making to support the choice of the best treatment modality that leads to the minimal number of adverse ...


Design And Synthesis Of Cpg-Lytic Peptide Conjugate, Brachytherapy Beads And A Combinatorial Library Of Primary Amines Used As Potential Therapeutics In The Treatment Of Cancers, Josanne-Dee Woodroffe Nov 2017

Design And Synthesis Of Cpg-Lytic Peptide Conjugate, Brachytherapy Beads And A Combinatorial Library Of Primary Amines Used As Potential Therapeutics In The Treatment Of Cancers, Josanne-Dee Woodroffe

Graduate Theses and Dissertations

Cancer remains one of the most feared diseases affecting the modern world. Second to heart disease, it is the largest cause of deaths, affecting one in three persons. Cancer cells are formed when normal, healthy cells become damage, losing their normal regulatory mechanism that control cell growth. There are many different types and progression of these cancer cells that determine the type of treatment a patient receives. The primary focus of this dissertation is to propose three studies of anticancer agents. In Chapter one, a CpG-lytic peptide conjugate was designed to target receptors on the cell membrane to concentrate the ...


The Role Of Sgs1 And Exo1 In The Maintenance Of Genome Stability., Lillian Campos-Doerfler Nov 2017

The Role Of Sgs1 And Exo1 In The Maintenance Of Genome Stability., Lillian Campos-Doerfler

Graduate Theses and Dissertations

Genome instability is a hallmark of human cancers. Patients with Bloom’s syndrome, a rare chromosome breakage syndrome caused by inactivation of the RecQ helicase BLM, result in phenotypes associated with accelerated aging and develop cancer at a very young age. Patients with Bloom’s syndrome exhibit hyper-recombination, but the role of BLM and increased genomic instability is not fully characterized. Sgs1, the only member of the RecQ family of DNA helicases in Saccharomyces cerevisiae, is known to act both in early and late stages of homology-dependent repair of DNA damage. Exo1, a 5′–3′ exonuclease, first discovered to play ...


Disorder Levels Of C-Myb Transactivation Domain Regulate Its Binding Affinity To The Kix Domain Of Creb Binding Protein, Anusha Poosapati Nov 2017

Disorder Levels Of C-Myb Transactivation Domain Regulate Its Binding Affinity To The Kix Domain Of Creb Binding Protein, Anusha Poosapati

Graduate Theses and Dissertations

Intrinsically disordered proteins (IDPs) do not form stable tertiary structures like their ordered partners. They exist as heterogeneous ensembles that fluctuate over a time scale. Intrinsically disordered regions and proteins are found across different phyla and exert crucial biological functions. They exhibit transient secondary structures in their free state and become folded upon binding to their protein partners via a mechanism called coupled folding and binding. Some IDPs form alpha helices when bound to their protein partners. We observed a set of cancer associated IDPs where the helical binding segments of IDPs are flanked by prolines on both the sides ...


Mechanism Elucidation And Inhibitor Discovery Against Serine And Metallo-Beta-Lactamases Involved In Bacterial Antibiotic Resistance, Orville A. Pemberton Nov 2017

Mechanism Elucidation And Inhibitor Discovery Against Serine And Metallo-Beta-Lactamases Involved In Bacterial Antibiotic Resistance, Orville A. Pemberton

Graduate Theses and Dissertations

The emergence and proliferation of Gram-negative bacteria expressing β-lactamases is a significant threat to human health. β-Lactamases are enzymes that degrade the β-lactam antibiotics (e.g., penicillins, cephalosporins, monobactams, and carbapenems) that we use to treat a diverse range of bacterial infections. Specifically, β-lactamases catalyze a hydrolysis reaction where the β-lactam ring common to all β-lactam antibiotics and responsible for their antibacterial activity, is opened, leaving an inactive drug. There are two groups of β-lactamases: serine enzymes that use an active site serine residue for β-lactam hydrolysis and metalloenzymes that use either one or two zinc ions for catalysis. Serine ...


Thermodynamic And Kinetic Aspects Of Hen Egg White Lysozyme Amyloid Assembly, Tatiana Miti Nov 2017

Thermodynamic And Kinetic Aspects Of Hen Egg White Lysozyme Amyloid Assembly, Tatiana Miti

Graduate Theses and Dissertations

Deposition of protein fibers with a characteristic cross-β sheet structure is the molecular marker associated with human disorders ranging from Alzheimer's disease to type II diabetes and spongiform encephalopathy. Given the large number of non-disease related proteins and peptides that have been shown to form amyloid fibrils in vitro, it has been suggested that amyloid fibril formation represents a generic protein phase transition. In the last two decades it has become clear that the same protein/peptide can assemble into distinct morphologically and structurally amyloid aggregates depending on the solution conditions. Moreover, recent studies have shown that the early ...