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Articles 1 - 7 of 7
Full-Text Articles in Biochemistry
Investigating The Impact Of Small Molecule Ligands And The Proteostasis Network On Protein Folding Inside The Cell, Karan Hingorani
Investigating The Impact Of Small Molecule Ligands And The Proteostasis Network On Protein Folding Inside The Cell, Karan Hingorani
Doctoral Dissertations
The folded forms of most proteins are critical to their functions. Despite the complexity of the cellular milieu and the presence of high-risk deleterious interactions, there is a high level of fidelity observed in the folding process for entire proteomes. Two important reasons for this are the presence of the quality control machinery consisting of chaperones and degradation enzymes that work jointly to optimize the population of the folded state and interaction partners that re-enforce the functional state and add to the competitive advantage of an organism. While substantial effort has been directed to understand protein folding and interactions in …
Characterizing The Inhibition Of Katanin Using Tubulin Carboxy-Terminal Tail Constructs, Corey E. Reed
Characterizing The Inhibition Of Katanin Using Tubulin Carboxy-Terminal Tail Constructs, Corey E. Reed
Masters Theses
Understanding how the cellular cytoskeleton is maintained and regulated is important to elucidate the functions of many structures such as the mitotic spindle, cilia and flagella. Katanin p60, microtubule-severing enzymes from the ATPase associated with cellular activities (AAA+) family, has previously been shown in our lab to be inhibited by free tubulin as well as α- and β-tubulin carboxy-terminal tail (CTT) constructs. Here we investigate the inhibition ability of several different tubulin CTT sequences. We quantify the effect of the addition of these constructs on the severing and binding activity of katanin. We find that some constructs inhibit katanin better …
Control Of Proteolysis During The Caulobacter Cell Cycle, Joanne Lau
Control Of Proteolysis During The Caulobacter Cell Cycle, Joanne Lau
Doctoral Dissertations
Intracellular protein destruction is a carefully coordinated and timed regulatory mechanism that cells utilize to modulate growth, adaptation to environmental cues, and survival. In Caulobacter crescentus, a bacterium known for studies of bacterial cell division cycle, the response regulator CpdR couples phosphorylation events with the AAA+ protease ClpXP to provide punctuated degradation of crucial substrates involved in cell cycle regulation. CpdR functions like an adaptor to alter substrate choice by ClpXP, however it remains unclear how CpdR influences its multiple targets. In this thesis, we show that, unlike canonical ClpXP adaptors, CpdR alone does not strongly bind its substrate. …
Kinetic And Dynamic Insights Into The Substrate Interactions And Catalysis Of Factor Inhibiting Hif-1 (Fih-1), Cristina B. Martin
Kinetic And Dynamic Insights Into The Substrate Interactions And Catalysis Of Factor Inhibiting Hif-1 (Fih-1), Cristina B. Martin
Doctoral Dissertations
inhibiting HIF-1 (FIH-1) modulates the master regulator of hypoxia sensing, hypoxia inducible factor-1 (HIF-1), by transcriptional repression making it an attractive potential target for treatment of hypoxia-related diseases. Given that similar enzymes are present within the cell and that they have other important physiological roles, defining the therapeutic window by which it can be selectively targeted becomes an issue. Consequently, it’s necessary to have a deeper understanding of the substrate interactions in FIH-1 that contributes to catalysis as this is one avenue that can be explored for future therapeutic investigations. The overall goal of this dissertation is to gain kinetic …
Chemical Stability Of Curcumin: Structure And Activity Relationship (Sar) Study, Zheyuan Du
Chemical Stability Of Curcumin: Structure And Activity Relationship (Sar) Study, Zheyuan Du
Masters Theses
Over the past decades, numerous studies have shown that curcumin has potent biological activities. As a potential chemopreventing agent, curcumin was demonstrated to exert anti-cancer effects in both in vitro and in vivo studies. However, low bioavailability of curcumin limited human clinical trials and its application to be formulated as therapeutics. In this thesis, we will summarize the anti-cancer effects of curcumin in animal studies and clinical trials. In addition, an SAR study will be introduced to elucidate the mechanism of curcumin degradation at physiological pH. We synthesized various curcumin analogues and compared their stability in phosphate buffer using HPLC …
Exploring The Impact Of The E. Coli Proteostasis Network On The Folding Fate Of Proteins With Different Intrinsic Biophysical Properties, Kristine Faye R. Pobre
Exploring The Impact Of The E. Coli Proteostasis Network On The Folding Fate Of Proteins With Different Intrinsic Biophysical Properties, Kristine Faye R. Pobre
Doctoral Dissertations
The three-dimensional (3D) native structure of most proteins is crucial for their functions. Despite the complex cellular environment and the variety of challenges that proteins experience as they fold, proteins can still fold to their native states with high fidelity. The reason for this is the presence of the cellular proteostasis network (PN), consisting of molecular chaperones and degradation enzymes, that collaborates to maintain proteostasis, in which the necessary levels of functional proteins are optimized. Although extensive research has been carried out on the mechanisms of individual components of the proteostasis network, little is known about how these components contribute …
The Application Of Hydrogen/Deuterium Exchange And Covalent Labeling Coupled With Mass Spectrometry To Examine Protein Structure, Nicholas B. Borotto
The Application Of Hydrogen/Deuterium Exchange And Covalent Labeling Coupled With Mass Spectrometry To Examine Protein Structure, Nicholas B. Borotto
Doctoral Dissertations
Thorough insight into a protein’s structure is necessary to understand how it functions and what goes wrong when it malfunctions. The structure of proteins, however, is not easily analyzed. The analysis must take place under a narrow range of conditions or risk perturbing the very structure being probed. Furthermore, the wide diversity in size and chemistry possible in proteins significantly complicates this analysis. Despite this numerous methods have been developed in order to analyze protein structure. In this work, we demonstrate that mass spectrometry (MS)-based techniques are capable of characterizing the structure of particularly challenging proteins. This is done through …