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Full-Text Articles in Life Sciences

The Molecular Basis For Amino-Terminal Acetylation By Nat Proteins, Glen Liszczak Jan 2013

The Molecular Basis For Amino-Terminal Acetylation By Nat Proteins, Glen Liszczak

Publicly Accessible Penn Dissertations

Amino-terminal acetylation is a co-translational process that occurs on a majority of all eukaryotic proteins. This modification mediates a wide range of biological processes including but not limited to cellular apoptosis, enzyme regulation, protein localization and the N-end rule for protein degradation. The amino-terminal acetyltransferase (NAT) enzymes that catalyze this reaction are distinguished from one another on the basis of substrate specificity, which is dictated by the identity of the amino-terminal sequence of the substrate protein. The NatA complex harbors the greatest diversity for substrate selection and is responsible for acetylating a majority of all proteins that undergo this modification ...


Spectroscopic Studies Of Peptide-Membrane Interactions, Kathryn Blakey Dupont Jan 2013

Spectroscopic Studies Of Peptide-Membrane Interactions, Kathryn Blakey Dupont

Publicly Accessible Penn Dissertations

Understanding the structure-dynamics-function relationship is a fundamental motivation for studying how proteins fold. Over the past several decades, significant progress has been made in elucidating the folding energy landscapes and dynamics of soluble, globular proteins. In contrast, the folding kinetics and mechanisms of membrane proteins are much less studied and understood, due in part to the fact that they reside in the heterogeneous and complex membrane environment. To provide new mechanistic insights into membrane protein folding, herein we studied the folding kinetics of the influenza hemagglutinin fusion peptide (HAfp), which folds into a representative helix-turn-helix structure in model membranes. Our ...


Magnetic Field Effects On Molecular Emissivity In Solutions, Tomoyasu Mani Jan 2013

Magnetic Field Effects On Molecular Emissivity In Solutions, Tomoyasu Mani

Publicly Accessible Penn Dissertations

Control over dynamics of excited states of molecules is fundamental to utilization of these states in all areas of technologies, including optical microscopy and tomography. We explored the possibility of magnetically controlling molecular emissivity by influencing spin dynamics in radical pairs (RPs) and triplet-triplet pair. We envisioned that by including RPs into a pathway leading to the formation (or decay) of an emissive triplet state, magnetic influence on phosphorescence could be realized via modulation of the RP's spin dynamics. RPs can initially be produced in their singlet or triplet spin state. These two cases were explored in the studies ...


Investigations Of Bioactivity, Disposition, And Metabolism Of Lipids Through Liquid Chromatography-Mass Spectrometry, Nathaniel W. Snyder Jan 2013

Investigations Of Bioactivity, Disposition, And Metabolism Of Lipids Through Liquid Chromatography-Mass Spectrometry, Nathaniel W. Snyder

Publicly Accessible Penn Dissertations

Inflammatory diseases and multiple human cancers are associated with increased cyclooxygenase-2 (COX-2) expression together with decreased expression of 15-hydroxyprostaglandin dehydrogenase (15-PGDH). This has been hypothesized to lead to a milieu of bioactive lipids modulating angiogenesis and cellular proliferation. Further insight into these processes were gained by traditional cell and molecular biology approaches, which were combined with cutting edge liquid chromatography mass spectrometry (LC-MS) methods to elucidate the function, disposition, and metabolism of a major COX-2/15-PGDH derived metabolite, 11-oxo-eicosatetraenoic acid (11-oxo-ETE). 11-oxo-ETE was found to possess significant anti-proliferative activity (IC50 2 microM) in human umbilical endothelial cells (HUVECS), which was ...


Large Protein Folding And Dynamics Studied By Advanced Hydrogen Exchange Methods, Benjamin Thomas Walters Jan 2013

Large Protein Folding And Dynamics Studied By Advanced Hydrogen Exchange Methods, Benjamin Thomas Walters

Publicly Accessible Penn Dissertations

Protein folding studies over the past 50 years have been largely focused on small proteins (< 200 residues) leading to a dearth of information about large protein folding. Regardless of protein size, research has generally lacked the structural tools with necessary temporal resolution to provide mechanistic insight into the process. This goal requires incisive information on transient kinetic intermediate conformations that describe the folding pathway. In this work special challenges that hinder large protein folding studies are addressed, and advancements to both HX NMR and HX MS experiments are described that provide unparalleled temporal resolution of structure formation than has been previously possible. These various advanced hydrogen exchange methods are used to study folding behaviors of the large, 370-residue, two-domain maltose binding protein from E. coli and provide a description of its folding pathway in structural detail. This work sheds light on two basic unresolved problems regarding the mechanisms of protein folding, the first being the enigmatic nature of the initial folding collapse event seen in many proteins, and the second concerning the nature of the folding pathway. We find that from an initially heterogeneous hydrophobic collapse, an obligatory intermediate emerges with a 7-second time constant followed by an apparent sequential pathway to the native state. These results add the largest protein studied at structural resolution to-date to the list of proteins known to fold through obligatory, native-like intermediates in distinct pathways and this work highlights strategies that may be employed to interrogate other large systems in future work.


Association Of Protein Helices And Assembly Of Foldamers: Stories In Membrane And Aqueous Environments, Shaoqing Zhang Jan 2013

Association Of Protein Helices And Assembly Of Foldamers: Stories In Membrane And Aqueous Environments, Shaoqing Zhang

Publicly Accessible Penn Dissertations

Solvents play an important role in association and assembly of molecules. Here we studied solvent effects on proteins and organic chemicals in different contexts. First, X-ray crystal structures show that helix dimers in membrane- and water-soluble proteins have distinct behaviors in packing and sequence selection. Transmembrane dimers are stabilized by compact packing and hydrogen bonding between small residues. Meanwhile, water-soluble dimers utilize hydrophobic residues for packing irrespective of the size of the interface and tight dimers are rare. Secondly, we apply the results learned above to a complex system in which a designed protein binds to single-walled carbon-nanotube in aqueous ...


N-Terminal Protein Modification By Aminoacyl Transferase: Enzymology And Applications., Anne Wagner Jan 2013

N-Terminal Protein Modification By Aminoacyl Transferase: Enzymology And Applications., Anne Wagner

Publicly Accessible Penn Dissertations

Protein modification is an important tool for understanding how a protein moves, folds, and operates in its cellular environment. We aim for a minimalist approach to protein modification in order to learn more about the protein while not perturbing its native state. Our method for ligation of small molecules to proteins has high N-terminal specificity and creates natural amide bond linkages under mild conditions. We utilized E. coli aminoacyl L/F transferase (AaT) in our ligation reaction to recognize a small synthetic substrate analog, which mimics aminoacylated tRNA, and can be chemically synthesized in only three steps. We have studied ...