Open Access. Powered by Scholars. Published by Universities.®
Physical Sciences and Mathematics Commons™
Open Access. Powered by Scholars. Published by Universities.®
- Keyword
-
- Bioinformatics (2)
- 2AP (1)
- ATP (1)
- Abasic site (1)
- Anti-Toxin (1)
-
- Biomarker (1)
- Clostridium Difficile (1)
- Clostridium difficile (1)
- Crosslinking (1)
- Disulfide bond (1)
- Drug Design (1)
- GPI anchoring (1)
- GPI transamidase (1)
- GlmS (1)
- Hfq (1)
- Hfq-RNA Interactions (1)
- In vitro assays for GPI-T (1)
- Kinases (1)
- Molecular Dynamics (1)
- Negative regulator (1)
- Nucleic Acid Enzymes (1)
- P53 (1)
- PC (1)
- Peptide inhibitors (1)
- Phosphorylation (1)
- Post-translation modifications (1)
- Protein design (1)
- Protein engineering (1)
- Regulatory RNA (1)
- Riboswitch (1)
- Publication
- Publication Type
Articles 1 - 10 of 10
Full-Text Articles in Physical Sciences and Mathematics
Carcinogenic Adducts Induce Distinct Dna Polymerase Binding Orientations, Kyle B. Vrtis, Radoslaw P. Markiewicz, Louis J. Romano, David Rueda
Carcinogenic Adducts Induce Distinct Dna Polymerase Binding Orientations, Kyle B. Vrtis, Radoslaw P. Markiewicz, Louis J. Romano, David Rueda
Chemistry Faculty Research Publications
DNA polymerases must accurately replicate DNA to maintain genome integrity. Carcinogenic adducts, such as 2-aminofluorene (AF) and N-acetyl-2-aminofluorene (AAF), covalently bind DNA bases and promote mutagenesis near the adduct site. The mechanism by which carcinogenic adducts inhibit DNA synthesis and cause mutagenesis remains unclear. Here, we measure interactions between a DNA polymerase and carcinogenic DNA adducts in real-time by single-molecule fluorescence. We find the degree to which an adduct affects polymerase binding to the DNA depends on the adduct location with respect to the primer terminus, the adduct structure and the nucleotides present in the solution. Not only do the …
Investigating Hfq-Mrna Interactions In Bacteria, Martha Audra Faner
Investigating Hfq-Mrna Interactions In Bacteria, Martha Audra Faner
Wayne State University Dissertations
Regulatory RNAs (sRNAs) are essential for bacteria to thrive in diverse environments and they also play a key role in virulence [11]. Trans-sRNAs affect the stability and/or translation of their target mRNAs through complementary base-pairing. The base-pairing interaction is not perfect and requires the action of an RNA binding protein, Hfq. Hfq facilitates these RNA-RNA interactions by stabilizing duplex formation, aiding in structural rearrangements, increasing the rate of structural opening, and/or by increasing the rate of annealing [18-21]. Hfq has two well characterized binding surfaces: the proximal surface, which binds AU rich stretches typical of sRNAs, and the distal surface, …
Single-Molecule Studies Of Local And Global Nucleic-Acid Dynamics, Eric Muthuri Patrick
Single-Molecule Studies Of Local And Global Nucleic-Acid Dynamics, Eric Muthuri Patrick
Wayne State University Dissertations
Nucleic acids undergo both global and local conformational changes that are important for their function. Structural studies have over the decades been invaluable in elucidation of various biomolecular mechanisms, hence contributing significantly to the understanding of biological events. However, a clear understanding of how molecules function in the cellular context requires investigation of their interconversion between multiple conformations, including mapping the folding landscape and any coupled changes in conformation. Work in this thesis focuses on fluorescence experiments, mainly at a single-molecule level to investigate such processes.
First, a novel single-molecule approach is described focusing on local dynamics within nucleic acids …
Disulfide By Design 2.0: A Web-Based Tool For Disulfide Engineering In Proteins, Douglas B. Craig, Alan A. Dombkowski
Disulfide By Design 2.0: A Web-Based Tool For Disulfide Engineering In Proteins, Douglas B. Craig, Alan A. Dombkowski
Wayne State University Associated BioMed Central Scholarship
Abstract
Background
Disulfide engineering is an important biotechnological tool that has advanced a wide range of research. The introduction of novel disulfide bonds into proteins has been used extensively to improve protein stability, modify functional characteristics, and to assist in the study of protein dynamics. Successful use of this technology is greatly enhanced by software that can predict pairs of residues that will likely form a disulfide bond if mutated to cysteines.
Results
We had previously developed and distributed software for this purpose: Disulfide by Design (DbD). The original DbD program has been widely used; however, it has a number …
Development Of Peptide Inhibitors Targeting Clostridium Difficile Toxins A/B And Characterizing The Regulatory Role Of A Putative Negative Regulator Tcdc In Clostridium Difficile Toxin Gene Expression, Sanofar Jainul Abdeen
Development Of Peptide Inhibitors Targeting Clostridium Difficile Toxins A/B And Characterizing The Regulatory Role Of A Putative Negative Regulator Tcdc In Clostridium Difficile Toxin Gene Expression, Sanofar Jainul Abdeen
Wayne State University Dissertations
Clostridium difficile infections cause one of the most common and vital hospitalacquired
diseases often associated with broad-spectrum antibiotic usage. TcdA and TcdB
are the key virulence factors involved in major patho-physiology. While standard
antibiotics provide some respite, due to the high relapse rates and the emergence of more
severe disease presentations, antibiotics alone have often proven to be suboptimal.
Therefore there is a desperate need to develop an effective non-antimicrobial
therapeutics. Part of this work focuses on identification and further characterization of
peptide therapeutic that target the major virulence factor TcdA/TcdB. Towards
development of mechanistic-based anti-toxin agent, phage display was …
Development And Optimization Of The First High Throughput In Vitro Fret Assay To Characterize The Saccharomyces Cerevisiae Gpi-T, Sandamali Amarasingha Ekanayaka
Development And Optimization Of The First High Throughput In Vitro Fret Assay To Characterize The Saccharomyces Cerevisiae Gpi-T, Sandamali Amarasingha Ekanayaka
Wayne State University Dissertations
DEVELOPMENT AND OPTIMIZATION OF AN IN VITRO FRET ASSAY TO CHARACTERIZE THE SACCHAROMYCES CEREVISIAE GPI TRANSAMIDASE
By
SANDAMALI AMARASINGHA EKANAYAKA
December 2013
Advisor: Dr. Tamara L. Hendrickson
Major: Biochemistry
Degree: Doctor of Philosophy
The enzyme glycosylphosphatidylinositol transamidase (GPI-T) mediates the attachment of a glycosylphosphatidylinositol (GPI) anchor to the C-terminus of specific proteins to produce GPI anchored proteins. This post-translational modification is essential for viability of eukaryotic organisms. However, very little is known about GPI-T and its catalytic activity. Thus, the research described in this abstract was conducted to develop an in vitro assay to monitor GPI-T. A high-throughput assay for …
Synthesis And Application Of Atp Analogs For Phosphorylation-Dependent Kinase-Substrate Crosslinking, Satish Kumar Garre Venkata Raghavendra
Synthesis And Application Of Atp Analogs For Phosphorylation-Dependent Kinase-Substrate Crosslinking, Satish Kumar Garre Venkata Raghavendra
Wayne State University Dissertations
Phosphorylation is an important post-translational modification that plays a key role in a variety of signaling cascades and cellular functions. Kinases phosphorylate protein substrates in a highly regulated manner and are promiscuous. Understanding kinase-substrate specificity has been challenging and there is a need for new chemical tools. To this end we developed -phosphate modified ATP photocrosslinking analogs ATP-ArN3 and ATP-BP, that crosslink substrate and kinase in a phosphorylation dependent manner. We have successfully demonstrated that ATP-ArN3 and ATP-BP can be used with natural kinase and substrates using cell lysates in vitro. We used our approach to identify novel kinases of …
Single-Stranded Dna Scanning And Deamination With Single-Molecule Resolution, Padhuk Gamarala Senavirathne
Single-Stranded Dna Scanning And Deamination With Single-Molecule Resolution, Padhuk Gamarala Senavirathne
Wayne State University Dissertations
SINGLE-STRANDED DNA SCANNING AND DEAMINATION WITH SINGLE-MOLECULE RESOLUTION
by
GAYAN SENAVIRATHNE
December 2013
Advisor: Dr. David Rueda & Dr.Ashok Bhagwat
Major: Chemistry (Analytical)
Degree: Doctor of Philosophy
APOBEC3G (Apo3G) and Activation-Induced cytidine Deaminase (AID) are the most notable members of APOBEC enzymes, a family of cytidine (C) deaminases with crucial functions in the immune system. In T cells, Apo3G deaminates C in viral cDNA to halt the replication of HIV 1 strains lacking viral infectivity factor (vif). In B cells, AID is required for the diversification of antibodies through initiation of somatic hypermutation (SHM), and class switch recombination (CSR), by …
Computational Approaches To Anti-Toxin Therapies And Biomarker Identification, Rebecca Jane Swett
Computational Approaches To Anti-Toxin Therapies And Biomarker Identification, Rebecca Jane Swett
Wayne State University Dissertations
This work describes the fundamental study of two bacterial toxins with computational methods, the rational design of a potent inhibitor using molecular dynamics, as well as the development of two bioinformatic methods for mining genomic data.
Clostridium difficile is an opportunistic bacillus which produces two large glucosylating toxins. These toxins, TcdA and TcdB cause severe intestinal damage. As Clostridium difficile harbors considerable antibiotic resistance, one treatment strategy is to prevent the tissue damage that the toxins cause. The catalytic glucosyltransferase domain of TcdA and TcdB was studied using molecular dynamics in the presence of both a protein-protein binding partner and …
Spliceosomal Prp24 Unwinds A Minimal U2/U6 Complex From Yeast, Chandani Manoja Warnasooriya
Spliceosomal Prp24 Unwinds A Minimal U2/U6 Complex From Yeast, Chandani Manoja Warnasooriya
Wayne State University Theses
Splicing plays a major role in eukaryotic gene expression by processing pre-mRNA to form mature mRNA. Pre-mRNAs undergo splicing to remove introns, non–protein coding regions, and religate exons, protein coding regions. This process is catalyzed by the spliceosome, which consists of five small nuclear ribonucleoprotein particles (snRNPs: U1, U2, U4, U5 and U6) and numerous protein factors. Proper assembly of spliceosomal components is critical for function, and thus, defects in assembly can be lethal. Several spliceosomal proteins facilitate structural rearrangements important for spliceosomal assembly and function. Prp24 is an essential factor in U6 snRNP assembly, and it has been proposed …