Biochemistry, Biophysics, and Structural Biology Commons^™

In Silico Characterization Of Protein-Protein Interactions Mediated By Short Linear Motifs, Heidy Elkhaligy

FIU Electronic Theses and Dissertations

Short linear motifs (SLiMs), often found in intrinsically disordered regions (IDPs), can initiate protein-protein interactions in eukaryotes. Although pathogens tend to have less disorder than eukaryotes, their proteins alter host cellular function through molecular mimicry of SLiMs. The first objective was to study sequence-based structure properties of viral SLiMs in the ELM database and the conservation of selected viral motifs involved in the virus life cycle. The second objective was to compare the structural features for SliMs in pathogens and eukaryotes in the ELM database. Our analysis showed that many viral SliMs are not found in IDPs, particularly glycosylation motifs. …

The Role Of Conformational Changes In Viral And Bacterial Protein Functions, Md Lokman Hossen

FIU Electronic Theses and Dissertations

Proteins do versatile work in cells. They require a cascade of structural changes to perform different tasks like binding to the other neighboring biomolecules, transporting small chemicals, activating a chemical reaction, etc. The structural conformations of proteins can be critical in changing their working ability. In this dissertation, I investigated the role of conformational changes of viral protein, e.g., spike and envelope protein of SARS-CoV-2, and bacterial protein, e.g., multidrug transporter and toxic extrusion protein- PfMATE from Pyrococcus furiosus. Also, I performed molecular docking-based drug screening targeting the E protein to suggest a set of drugs that can be repurposed …

Conformational Dynamics Of Biomolecules By Trapped Ion Mobility Spectrometry Dynamics, Juan Camilo Molano-Arévalo

FIU Electronic Theses and Dissertations

One of the main goals in structural biology is to understand the folding mechanisms and three-dimensional structure of biomolecules. Many biomolecular systems adopt multiple structures as a function of their microenvironment, which makes them difficult to be characterized by traditional structural biology tools (e.g., NMR, X-ray crystallography). As an alternative, complementary tools that can capture and sample multiple conformations needed to be developed. In the present work, we pioneered the application of a new variant of ion mobility spectrometry, trapped ion mobility spectrometry (TIMS), which provides high mobility resolving power and the possibility to study kinetically trapped intermediates as a …

Biochemical Characterization Of Arsi: A Novel C-As Lyase For Degradation Of Environmental Organoarsenicals, Shashank Suryakant Pawitwar

FIU Electronic Theses and Dissertations

Organoarsenicals such as methylarsenical methylarsenate (MAs(V)) and aromatic arsenicals including roxarsone (4-hydroxy-3-nitrophenylarsenate or Rox(V)) have been extensively used as an herbicide and growth enhancers in animal husbandry, respectively. They undergo environmental degradation to more toxic inorganic arsenite (As(III)) that contaminates crops and drinking water. We previously identified a bacterial gene (arsI) responsible for aerobic MAs(III) demethylation. The gene product, ArsI, is a Fe(II)-dependent extradiol dioxygenase that cleaves the carbon-arsenic (C-As) bond in MAs(III) and trivalent aromatic arsenicals. The objective of this study was to elucidate the ArsI mechanism. Using isothermal titration calorimetry, we determined the dissociation constants (Kd) and ligand-to-protein …

Protein-Ligand Interactions And Allosteric Regulation Of Activity In Dream Protein, Walter G. Gonzalez

FIU Electronic Theses and Dissertations

Downstream regulatory antagonist modulator (DREAM) is a calcium sensing protein that co-assembles with K_V4 potassium channels to regulate ion currents as well as with DNA in the nucleus, where it regulates gene expression. The interaction of DREAM with A-type K_V4 channels and DNA has been shown to regulate neuronal signaling, pain sensing, and memory retention. The role of DREAM in modulation of pain, onset of Alzheimer’s disease, and cardiac pacemaking has set this protein as a novel therapeutic target. Moreover, previous results have shown a Ca²⁺ dependent interaction between DREAM and K_V4/DNA involving …

Nuclear Magnetic Resonance Spectroscopic And Computational Investigations Of Chloroperoxidase Catalyzed Regio- And Enantio-Selective Transformations, Rui Zhang

FIU Electronic Theses and Dissertations

Chloroperoxidase (CPO) is the most versatile heme-containing enzyme that catalyzes a broad spectrum of reactions. The remarkable feature of this enzyme is the high regio- and enantio-selectivity exhibited in CPO-catalyzed oxidation reactions. The aim of this dissertation is to elucidate the structural basis for regio- and enantio-selective transformations and investigate the application of CPO in biodegradation of synthetic dyes.

To unravel the mechanism of CPO-catalyzed regioselective oxidation of indole, the dissertation explored the structure of CPO-indole complex using paramagnetic relaxation and molecular modeling. The distances between the protons of indole and the heme iron revealed that the pyrrole ring of …