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Full-Text Articles in Physical Sciences and Mathematics

Ferritin: Mechanistic Studies And Electron Transfer Properties, Bo Zhang Aug 2006

Ferritin: Mechanistic Studies And Electron Transfer Properties, Bo Zhang

Theses and Dissertations

Ferritins are ubiquitous iron storage proteins in living systems. Although much is known about the iron deposition process in ferritin and a mechanism has been developed, several important issues still remain unknown. One lingering question is the less than stoichiometric quantities of hydrogen peroxide detected in previous studies on animal ferritins. Extensive experimental data on identifying the species in competition for peroxide equivalents point to a surprising conclusion that H2O2 generated in the ferroxidase reaction is consumed by amine buffers that are commonly employed in in vitro ferritin studies, while non-nitrogen containing buffers, such as acetate, phosphate, and carbonate, do …


Crystallographic Analysis And Kinetic Studies Of Hiv-1 Protease And Drug-Resistant Mutants, Yunfeng Tie Jun 2006

Crystallographic Analysis And Kinetic Studies Of Hiv-1 Protease And Drug-Resistant Mutants, Yunfeng Tie

Chemistry Dissertations

HIV-1 protease is the most effective target for drugs to treat AIDS, however, the long-term therapeutic efficiency is restricted by the rapid development of drug resistant variants. To better understand the molecular basis of drug resistance, crystallographic and kinetic studies were applied to wild-type HIV-1 protease (PR) and drug-resistant mutants, PRV82A, and PRI84V, in complex with substrate analogues, the current drug saquinavir and the new inhibitor UIC-94017 (TMC-114). UIC-94017 was also studied with mutants PRD30N and PRI50V. The drug-resistant mutations V82A, I84V, D30N and I50V participate in substrate binding. Eighteen crystal structures were refined at resolutions of 0.97-1.60A. The high …


Kinetic And Spectroscopic Characterization Of The E134a- And E134d-Altered Dape-Encoded N-Succinyl-L,L-Diaminopimelic Acid Desuccinylase From Haemophilus Influenzae, Ryan S. Davis, David L. Bienvenue, Sabina I. Swierczek, Danuta M. Gilner, Lakshman Rajagopal, Brian Bennett, Richard C. Holz Mar 2006

Kinetic And Spectroscopic Characterization Of The E134a- And E134d-Altered Dape-Encoded N-Succinyl-L,L-Diaminopimelic Acid Desuccinylase From Haemophilus Influenzae, Ryan S. Davis, David L. Bienvenue, Sabina I. Swierczek, Danuta M. Gilner, Lakshman Rajagopal, Brian Bennett, Richard C. Holz

Physics Faculty Research and Publications

Glutamate-134 (E134) is proposed to act as the general acid/base during the hydrolysis reaction catalyzed by the dapE-encoded N-succinyl-l,l-diaminopimelic acid desuccinylase (DapE) from Haemophilus influenzae. To date, no direct evidence has been reported for the role of E134 during catalytic turnover by DapE. In order to elucidate the catalytic role of E134, altered DapE enzymes were prepared in which E134 was substituted with an alanine and an aspartate residue. The Michaelis constant (K m) does not change upon substitution with aspartate but the rate of the reaction changes drastically in the following order: glutamate (100% …


Chemometric Analysis Of Multivariate Liquid Chromatography Data: Applications In Pharmacokinetics, Metabolomics, And Toxicology, Sarah Elizabeth Graham Porter Jan 2006

Chemometric Analysis Of Multivariate Liquid Chromatography Data: Applications In Pharmacokinetics, Metabolomics, And Toxicology, Sarah Elizabeth Graham Porter

Theses and Dissertations

In the first part of this work, LC-MS data were used to calculate the in-vitro intrinsic clearances (CLint) for the metabolism of p-methoxyrnethamphetamine (PMMA) and fluoxetine by the CYP2D6 enzyme using a steady-state (SS) approach and a new general enzyme (GE) screening method. For PMMA, the SS experiment resulted in a CLint of 2.7 ± 0.2 µL pmol 2D6-1min-1 and the GE experiment resulted in a CLint of 3.0 ± 0.6 µL pmol 2D6-1min-1. For fluoxetine, the SS experiment resulted in a CLint of 0.33 ± 0.17 µL pmol 2D6-1min-1 and the GE experiment resulted in a CLint of 0.188 …