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Chemistry

NMR

Legacy Theses & Dissertations (2009 - 2024)

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Full-Text Articles in Physical Sciences and Mathematics

Modeling Chaperone-Substrate Interactions Of Alpha Crystallin From The Ocular Lens, Lisa Marie S. Ramirez Jan 2019

Modeling Chaperone-Substrate Interactions Of Alpha Crystallin From The Ocular Lens, Lisa Marie S. Ramirez

Legacy Theses & Dissertations (2009 - 2024)

The α-crystallins (αA- and αB-crystallin isoforms) from the ocular lens are small heat shock proteins and molecular chaperones, widely believed to play a significant role in protecting the lens from cataract. Mutations and modifications on human αA- and αB-crystallin (HAA and HAB, respectively) are linked to a variety of diseases, including cataract formation, neuropathological protein folding disorders, and many others. It is believed that HAA and HAB prevent the aggregation of other lens proteins. However, the structural and thermodynamic details of the chaperone-substrate (aka “client”) interaction are sparse. Therefore, the main objective of this dissertation is to reveal structural and …


Structural Characterization Of The Interactions Of Nicotinamide And Analogs With Human Sirt6 By Saturation Transfer Difference (Std) Nmr And Site Directed Mutagenesis, Beatriz Elena Bolivar-Vega Jan 2017

Structural Characterization Of The Interactions Of Nicotinamide And Analogs With Human Sirt6 By Saturation Transfer Difference (Std) Nmr And Site Directed Mutagenesis, Beatriz Elena Bolivar-Vega

Legacy Theses & Dissertations (2009 - 2024)

The allosteric regulation of SIRT6 by nicotinamide (NAM), along with the growing evidence of this enzyme's key role in the immune response, prompted the mechanistic study of SIRT6 inhibition by pyrazinamide (PZA) and analogs. In our current study, PZA, an analog of NAM, was revealed to have a modest modulatory effect on SIRT6, an enzyme that regulates the NF-κB signaling pathway at the transcriptional level (a relevant pathway to inflammation). Similarly, the analogs of PZA, 5-Cl PZA, 5-MeO PZA, and POA exhibited a modulatory effect against SIRT6 in our in vitro studies, enabling identification of a potential new target for …


Homologous And Heterologous Crystallin Protein Interactions As The Molecular Basis Of Inherited Cataract, Priya Ranjan Banerjee Jan 2011

Homologous And Heterologous Crystallin Protein Interactions As The Molecular Basis Of Inherited Cataract, Priya Ranjan Banerjee

Legacy Theses & Dissertations (2009 - 2024)

Age-related cataract is the most common cause of blindness worldwide. Nearly fifty percent of Americans above the age of 75 are diagnosed with this disease (http://www.nei.nih.gov/eyedata/pbd_tables.asp), and surgical intervention is the sole method of treatment at present (http://www.nei.nih.gov/healthyvision/objective/cataracts.asp). In the developing world, even this treatment is not readily available. These are compelling reasons to search for better treatments to delay, prevent or arrest cataract formation. Recent evidence suggests that age-related cataracts also have a genetic component. Therefore, determining the mechanisms underlying genetic cataracts with a known association to a protein-mutation is one important strategy towards understanding the molecular basis for …


In-Cell And In Vitro Studies Of Disease Related Protein-Protein Interactions Using Nmr-Spectroscopy, Andres Yudiel Maldonado Jan 2011

In-Cell And In Vitro Studies Of Disease Related Protein-Protein Interactions Using Nmr-Spectroscopy, Andres Yudiel Maldonado

Legacy Theses & Dissertations (2009 - 2024)

The receptor for advanced glycation end products (RAGE) is a multiligand cell surface macromolecule that plays a central role in the etiology of diabetes, inflammation, and neurodegeneration. The cytoplasmic domain of RAGE, ctRAGE, is critical for RAGE-dependent signal transduction. As the most membrane proximal event, mDia1 binds to ctRAGE and is essential for RAGE ligand-stimulated phosphorylation of AKT and cell proliferation/migration. We show that ctRAGE contains an unusual alpha-turn that mediates the mDia1-ctRAGE interaction and is required for RAGE dependent signaling. The results establish a novel mechanism through which an extracellular signal initiated by RAGE ligands regulates RAGE signaling in …


Structural Interactions And Dynamics Of Disease Related Proteins By Using Nmr Spectroscopy, Shadakshara Swamy Puttamadappa Jan 2011

Structural Interactions And Dynamics Of Disease Related Proteins By Using Nmr Spectroscopy, Shadakshara Swamy Puttamadappa

Legacy Theses & Dissertations (2009 - 2024)

Nuclear Magnetic Resonance (NMR) is a powerful spectroscopic technique to study the structure, molecular interactions, and dynamics of proteins. Modern NMR instrumentation, advancements in experimental techniques and revolutionary developments in recombinant DNA technology have made NMR a versatile and very convenient tool for biomolecule characterization.