Biochemistry Commons^™

Predicting The Structure And Selectivity Of Coiled-Coil Proteins, Mojtaba Jokar

Wayne State University Dissertations

A coiled-coil protein structure consists of two (in coiled-coil dimers) or more interacting α-helical strands that together form a left-handed supercoil structure. Many coiled-coil proteins are involved in significant biological functions such as the regulation of gene expression, known as transcription factors. Also coiled-coil structures entail unique mechanical properties critical to the function and integrity of various motor proteins, cytoskeletal filaments and extra-cellular matrix proteins. Engineering these transcription factors is also expected to create more efficient and practical solutions to treat neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), amyotrophic lateral sclerosis (ALS) and prion …

Alternative Strategies To Inhibit Lysine Methyltransferases And Deubiquitinases In Human Cancers, Nicholas Spellmon

Wayne State University Dissertations

X-ray crystallography is the gold standard method for imagining macromolecules to atomic resolution. Three dimensional data is central to understanding the molecular mechanism how DNA, RNA and proteins function in biological events. Structural insights into these events provide a molecular window to visualize how biological molecules influence human health. Visualizing the architecture of these molecules set the stage for rational and selective drug design. The following dissertation utilizes biochemical and biophysical tools, including X-ray crystallography, to shed light on poorly understood mechanisms related to SMYD2 activity and regulation, USP10 architecture and function, and PDZ-RhoGEF dimerization. SMYD2 is one member of …

Characterization Of Initial Iron Binding Location And The Structure/Iron Binding Site On S.Cerevisiae Isu And On D.Melanogaster Frataxin, Andria V. Rodrigues

Wayne State University Dissertations

Iron-induced free radical damage has been implicated in the pathology of diseases of iron overload such as Friedreich's Ataxia, a genetic disorder characterized by an accumulation of iron in actively metabolizing tissues ultimately leading to cardio- and neuro- degeneration and cell death. It is caused by an inability to synthesize the mitochondrial protein, frataxin. Frataxin has been shown by numerous groups to be a part of the iron-sulfur cluster (ISC) multicomplex, where it functions in the capacity of a potential iron provider and an allosteric modulator of both the cysteine desulfurase and scaffold protein ISU. My research has been focused …

Elucidation Of The Functional Role Of Pcbp-The Cytosolic Iron Chaperone Protein Family, In Cellular Iron Homeostasis, Poorna Subramanian

Wayne State University Dissertations

Biological Role of Ferritin - Iron is essential for life and often utilized as a cofactor in many proteins. In humans, iron accumulation causes cirrhosis, arthritis, cardiomyopathy and diabetes mellitus, and it is associated with increased risk of cancer and heart disease. In contrast, decreased brain iron content results in permanent neurocognitive and motor impairment. Intracellular iron content must be maintained within a narrow range to avoid the adverse effects of iron depletion or excess, and this function is performed by the protein ferritin. Ferritins are iron storage proteins that are ubiquitously expressed in animals, plants and bacteria. They serve …

"Fine-Tuning" Of Ribosomal Structure And Functions By Pseudouridylation And Rna-Protein Interactions, Jun Jiang

Wayne State University Dissertations

ABSTRACT

"Fine-tuning" of ribosomal structure and functions by pseudouridylation and RNA-protein interactions

by

JUN JIANG

AUGUST 2012

Advisor: Prof. John SantaLucia Jr.

Major: Chemistry (Biochemistry)

Degree: Doctor of Philosophy

Ribosomal structure and functions appear to be "fine-tuned" by pseudouridylation and RNA-protein interactions. Pseudouridylation may promote base stacking interactions by mediating the base stacking between residues on both sides. In the RNA duplex region, this enhanced stacking interaction contributes to stabilization of duplex folding. In the loop region, enhanced stacking in one structural motif may destabilize the conformation of adjacent structural residues. This hypothesis is supported by both UV-melting experiments, where …

Characterization Of Splicing Mechanisms By Single-Molecule Fluorescence, Krishanthi Sanjeewani Karunatilaka

Wayne State University Dissertations

Group II introns rank amongst the largest self-splicing ribozymes found in bacteria and organellar genomes of various eukaryotes. Despite the diversity in primary sequences, group II introns posses highly conserved secondary structures consisting of six domains (D1-D6). To perform its function, the large multidomain group II intron RNA must adopt the correctly folded structure. As a result, in vitro splicing of these introns requires high ionic strength and elevated temperatures. In vivo, this process is mainly assisted by protein cofactors. However, the exact mechanism of protein-mediated splicing of group II intron RNA is still not known.

In order to …