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Full-Text Articles in Life Sciences

Studies Into The Allosteric Regulation Of Adp-Glucose Pyrophosphorylases, Benjamin Luke Hill Jan 2016

Studies Into The Allosteric Regulation Of Adp-Glucose Pyrophosphorylases, Benjamin Luke Hill

Dissertations

The synthesis of glycogen in bacteria and starch in plants is allosterically controlled by the production of ADP-glucose by ADP-glucose pyrophosphorylase. Using computational studies, site directed mutagenesis, and kinetic characterization, and protein crystallography we found a critical region for transmitting the allosteric signal in the Escherichia coli and A. tumefaciens ADP-glucose pyrophosphorylase. Molecular dynamics simulations and structural comparisons with other ADP-glucose pyrophosphorylases provided information to hypothesize communication pathways that link allosteric and active sites, and this was tested by site-directed mutagenesis and kinetic characterization of the mutant enzymes. In addition, the application of x-ray crystallography enabled the pinpointing of the …


Development Of "Inside-Out" Pegylated Crosslinked Hemoglobin Polymers: Novel Hemoglobin-Based Oxygen Carriers (Hboc), Kyle Douglas Webster Jan 2016

Development Of "Inside-Out" Pegylated Crosslinked Hemoglobin Polymers: Novel Hemoglobin-Based Oxygen Carriers (Hboc), Kyle Douglas Webster

Dissertations

The development of an effective blood substitute is urgent due to increasingly common blood shortages, the need to type-match donated blood, and communicable diseases (e.g. HIV) posing risks for blood transfusions around the world. There have been many attempts at creating hemoglobin-based oxygen carriers (HBOC) using a variety of techniques centered around the use of polyethylene glycol (PEG) conjugated to hemoglobin (Hb) tetramers. A novel method, “Inside-Out” PEGylation, has been developed by our lab to produce a polyethylene glycol crosslinked hemoglobin (PEG XL-Hb) polymer. This method utilizes a single PEG backbone that is surrounded by multiple proteins, instead of covering …


Mechanistic Variations Of The Bronsted Linear Free Energy Relationships For Nonezymatic Nucleotidyl Transfer Reactions, Zheng Zhang Jan 2016

Mechanistic Variations Of The Bronsted Linear Free Energy Relationships For Nonezymatic Nucleotidyl Transfer Reactions, Zheng Zhang

Dissertations

As the essential enzymes in human bodies, DNA polymerases play a significant role in DNA replication, repair, genetic recombination, and reverse transcription. In 1956, the enzyme of DNA polymerase I, also named as Pol I, was discovered by Arthur Kornberg and colleagues. Subsequently, the Noble Committee had decided that the Noble Prize in Physiology or Medicine for 1959 was to be awarded to Kornberg for his excellent original work that describes the DNA replication process whereby the DNA polymerase copies the nucleotide sequence of a DNA template strand. Because of the complex enzyme structure in the DNA polymerase, it is …