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Full-Text Articles in Life Sciences
Investigating The Main Protease (Mpro) Of Sars-Cov-2 As A Potential Drug Target, Valerie Giovina Pascetta
Investigating The Main Protease (Mpro) Of Sars-Cov-2 As A Potential Drug Target, Valerie Giovina Pascetta
Honors Theses and Capstones
The rapid spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of the coronavirus disease 19 (COVID-19) pandemic has claimed the lives of roughly 6.2 million people worldwide as of May 2022. The virus’s main protease (Mpro ) has been identified as an attractive drug target due to the critical role it plays in the viral life cycle. The roughly 34 kDa Mpro cleaves functional viral polypeptides out of two long polyproteins at conserved cut sites, allowing them to fulfill their role in processes like transcription and replication. Here, we have studied the enzymatic activity …
Direct Single Molecule Imaging Of Enhanced Diffusion For Enzymes And Enzyme-Conjugated Dna Origami, Mengqi Xu
Direct Single Molecule Imaging Of Enhanced Diffusion For Enzymes And Enzyme-Conjugated Dna Origami, Mengqi Xu
Dissertations - ALL
Enzymes have been shown to diffuse faster in the presence of their substrates. Recently, we revealed new insights into this process of enhanced diffusion using single-particle tracking (SPT) with total internal reflection fluorescence (TIRF) microscopy. We found that the mobility of individual enzymes was enhanced three-fold in the presence of the substrate, and the motion remained Brownian. We showed that the relative increase in diffusion is independent of the total enzyme concentrations; and the oligomerization state of enzymes did not change during the catalytic turnover. These experiments ruled out the possibility that the enhanced enzyme diffusion was caused by the …
Deciphering The Catalytic Mechanism Of Human Manganese Superoxide Dismutase, Jahaun Azadmanesh
Deciphering The Catalytic Mechanism Of Human Manganese Superoxide Dismutase, Jahaun Azadmanesh
Theses & Dissertations
The livelihood of human cells is heavily dependent on the ability to modulate the presence of highly reactive oxygen-based molecules termed reactive oxygen species (ROS). In excess, ROS facilitate oxidative damage to the macromolecules of cellular life. SODs are the major family of antioxidant proteins that prevent the buildup of overwhelming amounts of ROS within cells. Sometimes dubbed the “first line of defense” against oxidative damage, SODs defend against the harmful accumulation of ROS by eliminating superoxide. Superoxide is a ROS itself that is also a precursor to much more harmful ROS molecules. MnSOD is the manganese containing form of …
Regulation Of Katanin Activity On Microtubules, Madison A. Tyler
Regulation Of Katanin Activity On Microtubules, Madison A. Tyler
Masters Theses
The cytoskeleton is a dynamic network of microtubules constantly being reorganized to meet the spatiotemporal demands of the cell. Microtubules are organized into subcellular highways to control cell processes such as cell division, cargo transport, and neuronal development and maintenance. Reorganization of this intricate network is tightly regulated by various stabilizing and destabilizing microtubule-associated proteins that decorate the network. Katanin p60 is a microtubule destabilizing enzyme from the ATPases Associated with various Activities (AAA+) family. It can both sever and depolymerize microtubules. In order to sever microtubules, katanin recognizes the tubulin carboxy-terminal tails (CTTs) and hydrolyzes ATP. Using super-resolution microscopy …
Insights From Molecular Dynamics On Substrate Binding And Effects Of Active Site Mutations In Delta1-Pyrroline-5-Carboxylate Dehydrogenase, Bogdan F. Ion, Mohamed M. Aboelnga, James W. Gauld
Insights From Molecular Dynamics On Substrate Binding And Effects Of Active Site Mutations In Delta1-Pyrroline-5-Carboxylate Dehydrogenase, Bogdan F. Ion, Mohamed M. Aboelnga, James W. Gauld
Chemistry and Biochemistry Publications
The NAD+-dependent enzyme, 1-pyrroline-5-carboxylate dehydrogenase (P5CDH), has an important role in proline and hydroxyproline catabolism for humans. Specifically, this aldehyde dehydrogenase is responsible for the oxidation of both L-glutamate- -semialdehyde (GSA) and 4-erythro-hydroxy-L-glutamate- -semialdehyde (4-OH-GSA) to their respective L-glutamate product forms. We have performed a detailed molecular dynamics (MD) study of both the reactant and product complex structures of P5CDH to gain insights into ligand binding (i.e., GSA, 4-OH-GSA, NAD+, GLU) in the active site. Moreover, our investigations were further extended to examine the structural impact of S352L, S352A, and E314A mutations on the deficiency in the P5CDH enzymatic activity. …
Rescuing Acetylcholinesterase From Nerve Agent Inhibition: Protein Dynamics Driven Drug Discovery, Aiyana M. Emigh, Brian Bennion
Rescuing Acetylcholinesterase From Nerve Agent Inhibition: Protein Dynamics Driven Drug Discovery, Aiyana M. Emigh, Brian Bennion
STAR Program Research Presentations
Severe morbidity and mortality consequences result from irreversible inhibition of human acetylcholinesterase by organophosphates (OPs). Oxime-based reactivators are currently the only available treatments but lack efficacy in the central nervous system (CNS) where the most damage occurs. Computational docking and molecular dynamics (MD) simulations reveal complex structural barriers that may reduce oxime efficacy. These results may guide future drug designs of more effective countermeasures.