Biochemistry Commons^™

The Classification Of An Unknown Protein 3h04, Britney Dyszel

Biochemistry and Molecular Biology Presentations

An unclassified protein in the Protein Data Bank, 3H04, was selected as a protein of interest. Research was performed in silico to gain key information on the structure, sequence, and homology of protein 3H04. This research was guided using the BASIL Project’s protocols on in silico research. Several databases were utilized to study protein 3H04. Based on the data gathered, unclassified protein 3H04 is an aminopeptidase that cleaves prolyl-dipeptidyl peptide bonds through alpha beta hydrolase function.

The Role Of Conformational Dynamics In Isocyanide Hydratase Catalysis, Medhanjali Dasgupta

Department of Biochemistry: Dissertations, Theses, and Student Research

Post-translational modification of cysteine residues can regulate protein function and is essential for catalysis by cysteine-dependent enzymes. Covalent modifications neutralize charge on the reactive cysteine thiolate anion and thus alter the active site electrostatic environment. Although a vast number of enzymes rely on cysteine modification for function, precisely how altered structural and electrostatic states of cysteine affect protein dynamics, which in turn, affects catalysis, remains poorly understood.

Here we use X-ray crystallography, computer simulations, site directed mutagenesis and enzyme kinetics to characterize how covalent modification of the active site cysteine residue in the enzyme, isocyanide hydratase (ICH), affects the protein …

Polyglucosan Body Structure In Lafora Disease, M. Kathryn Brewer, Jean-Luc Putaux, Alberto Rondon, Annette M. Uittenbogaard, Mitchell A. Sullivan, Matthew S. Gentry

Lafora Epilepsy Cure Initiative Faculty Publications

Abnormal carbohydrate structures known as polyglucosan bodies (PGBs) are associated with neurodegenerative disorders, glycogen storage diseases (GSDs), and aging. A hallmark of the GSD Lafora disease (LD), a fatal childhood epilepsy caused by recessive mutations in the EPM2A or EPM2B genes, are cytoplasmic PGBs known as Lafora bodies (LBs). LBs result from aberrant glycogen metabolism and drive disease progression. They are abundant in brain, muscle and heart of LD patients and Epm2a^-/- and Epm2b^-/- mice. LBs and PGBs are histologically reminiscent of starch, semicrystalline carbohydrates synthesized for glucose storage in plants. In this study, we define LB architecture, …

Characterization Of A Split-Nluc Assay For Monitoring Changes In Alpha-Synuclein Solubility In Living Cells, Baolong Truong

Honors Program: Senior Projects (Public)

Alpha-synuclein is the primary constituent of Lewy Bodies, protein aggregates associated with Parkinson’s Disease, Dementia with Lewy Bodies, and Multiple Systems Dystrophy. Given the terminal nature of these synucleinopathies, the need for an assay that can report on alpha-synuclein aggregation levels in living systems is critical. Western blotting represents one potential approach to this problem; however, this technique can often be limited by selectivity of available antibodies and experimental reproducibility. Herein, we describe a novel luminescence-based assay capable of detecting alpha-synuclein solubility in bacterial cells. This platform can report on the influence of disease-relevant mutations and small molecules. Antibodies are …

Probing The Function Of Perilipin 5b, Rebekah Dalton

Undergraduate Honors Thesis Projects

Many modern health issues arise from aberrant lipid metabolism, among these are type II diabetes and non-alcoholic fatty liver disease. One commonality these diseases share is neutral lipid metabolism and storage. Regulation of neutral lipid metabolism is of vital importance in the body, and among the proteins responsible for such regulation are the perilipins. Perilipins are a family of five conserved proteins that are found on the surface of lipid storage droplets and play a central role in the regulation of cellular neutral lipid metabolism. Perilipin 5 specifically, is expressed in tissues with a high capacity for fatty acid oxidation …

Characterization Of Drosophila Boundary Element Associated Factor Beaf-32b Interactions With Transcription Factors And Chromatin Remodeling Complexes., Yuankai Dong

LSU Doctoral Dissertations

BEAF (Boundary Element-Associated Factor) was originally identified as a chromatin domain insulator binding protein, suggesting that it might play a role in linking gene regulation to chromatin organization and dynamics. Genome-wide mapping found that BEAF is usually found near transcription start sites, often of housekeeping genes, suggesting that it might play a role in promoter function. This would be a nontraditional role for an insulator binding protein. To gain insight into molecular mechanisms of BEAF function, we identified proteins that interact with BEAF using yeast 2-hybrid assays. Here we focus on three identified transcription factors: Bcd, Scr and Sry-δ. Interactions …

Synthesis Of Novel Temozolomide-Fatty Acid Imide Hybrid Compounds For The Chemotherapeutic Treatment Of Glioblastoma Multiforme, Janice Pakkianathan

Honors Theses

Glioblastoma multiforme (GBM) is an aggressive form of brain cancer that originates from glial cells, which make up the supportive tissue surrounding neurons. Temozolomide (TMZ) is the current chemotherapeutic drug administered to treat GBM as it works to inhibit the growth of the cancer cells. This research study focused on developing a method for synthesizing novel hybrid compounds that combines TMZ with various fatty acids known to have anticancer properties, forming a series of imide compounds with potential chemotherapeutic effects. Before synthesizing the compounds, various methods for synthesizing an imide from a primary amide were tested to ensure that TMZ …

Fungicide Sensitivity Of Sclerotinia Sclerotiorum Isolates Selected From Five Different States That Use Different Fungicide Treatments, Cristian Wulkop Gil

UCARE: Research Products

Sclerotinia sclerotiorum is a plant pathogenic fungus that causes a disease called white mold that can infect more than 450 plant species including soybeans, dry beans, green beans, canola, and sunflower. This pathogen is capable of up to $252M in losses every year (U.S. Canola Association, 2014). Fungicides are widely used in developed agricultural systems to control disease. However, resistance to the most effective fungicides has emerged and spread in pathogen populations and there have been multiple reports of S. sclerotiorum isolates becoming resistant to certain fungicides. Since different fields in different states use different fungicide treatments on plants and …

Synthesis And Characterization Of Potential Pharmaceutical Analogs Of A Gvsu Lead Compound: An Investigation Of Antibiotic & Anti-Tumor Activity, Nicole Horne

Student Scholars Day Posters

In support of ongoing anti-microbial & anti-tumor research, analogs of a GVSU lead compound, a derivative of the known telomerase inhibitor BIBR1532, were synthesized. These compounds were submitted for biological analysis to determine pharmacological activity toward the discovery of either an antibiotic that can resist bacterial enzymatic degradation or a chemotherapeutic molecule that can destroy tumor cells without increasing toxicity. The anti-microbial interest in these compounds was based on the fact that they are non-penicillin based antibiotics and display a broad range of efficacy against targeted bacteria, including C. diff & MRSA, with minimal toxicity. These compounds were made via …

Periodic Table Club, Makayla Gill, Kailynn Jensen

Honors Program: Expanded Learning Clubs

This club is dedicated to teaching the generation of future scientists the periodic table. This is designed to be a unique take on a STEM club that uses the periodic table as a backbone for a solid foundation in chemistry.

Toxicity Of Novel Platinum Compounds In Mammalian Cancer Cells, Vanesa Veletanlic

Masters Theses & Specialist Projects

There are currently three FDA platinum compounds approved for use as chemotherapeutics, where each drug has variable efficacies for different cancer types depending on cancer’s tissue of origin. The approved compounds are platinum(II) complexes with four coordination sites on the platinum atom allowing two types of ligands to attach: leaving ligands, which are removed from the platinum atom in solution, and non-leaving ligands, which remain complexed to the platinum. Carboplatin, the preferred compound used to treat ovarian and small-cell lung cancers, has a characteristic cyclobutanedicarboxylic acid leaving ligand and two ammonia non-leaving ligands. A novel compound, 1,1-cyclobutanedicarboxylato(ethylenediamine)platinum (II), or Pt(en)CBDCA, …

Tip60 Regulation Of Δnp63Α Is Associated With Cisplatin Resistance, Akshay Hira, Andrew Stacy, Jin Zhang, Michael P. Craig, Madhavi Kadakia

Celebration of Undergraduate & Graduate Research, Scholarship, and Creative Activities Materials

About 5.4 million basal and squamous cell skin cancers are diagnosed every year in the US. ΔNp63a, a member of the p53 transcription factor family, is overexpressed in non-melanoma skin cancer and regulates cell survival, migration and invasion. TIP60 is histone acetyltransferase (HAT) which mediates cellular processes such as transcription and the DNA damage response (DDR). Previous studies in our lab have shown that overexpression of TIP60 induces ΔNp63a protein stabilization in a catalytic-dependent manner. Since ΔNp63a is known to transcriptionally regulate several DDR genes and promote cisplatin resistance, its stabilization by TIP60 may contribute to the failure of platinum-based …

Optimization Of Methods For Cross-Species Infection Of Cell Cultures With Wolbachia, Sarah J. Lane

Honors Thesis

The common intracellular endosymbiont genus of bacteria called Wolbachia is of interest due to the promise it shows for playing a role in disease control. Wolbachia have a number of widely variable effects on its many species of host insects. In combination with these roles, Wolbachia largely affects reproduction and development of its host species. It can lead to feminization and cytoplasmic incompatibility (Werren et al. 2008). Furthermore, this species is vertically transmitted which means that it passes from mother to offspring (Caragata et al., 2016). In combination with its effects on reproduction, which can allow Wolbachia to propagate through …

Synthesis And Structure-Activity Relationship Study Of Novel Nitrodiphenylurea Antibiotics, Helen Bahlbi

Student Scholars Day Posters

According to the World Health Organization, tuberculosis (TB) is the leading cause of death by infectious disease. Tuberculosis is caused by the bacteria Mycobacterium tuberculosis and occurs globally. Additionally, in 2017, TB was reported in all 50 states. Due to the scope of TB, strict observation of patients is required to ensure adherence to the current drug regimen. However, most reported cases are in developing countries where proper care is difficult. With the emergence of multidrug-resistant TB exhibiting resistance to current treatments, novel antibiotics are needed. Recently, our lab discovered a family of diphenyl ureas that exhibit antimicrobial activity against …

The Organic Synthesis Of Anthranilic Acid Derivatives As Potential Active Antibiotics, Paul Chappell

Student Scholars Day Posters

The objective of this research project was to synthesize multiple derivatives of anthranilic acid. These derivatives will then be tested for antibiotic activity against Staphylococcus aureus and Escherichia coli (E. coli). As bacteria become more resistant to penicillin-based antibiotics, the exploration of anthranilic acid-based antibiotics could serve an important role for future medical use. This research project included data collection via 1H-NMR, 12C-NMR, TLC, MP, and IR to determine purity for biological testing.

Network Approaches To Elucidate The Determinants Of Protein Topology And Stability, Zeinab Haratipour

Chemistry & Biochemistry Theses & Dissertations

Predicting three-dimensional structures of proteins from sequence information alone, remains one of the most profoundly challenging and intensely studied problems in basic science. It has uniquely garnered the interdisciplinary efforts of biologists, biochemists, computer scientists, mathematicians and physicists. The advancement of computational methods to study fundamental features of proteins also enables insights that are either difficult to explore experimentally or complimentary to further interpret experimental data. In the present research and through the combined development and application of molecular dynamics and network science approaches we aimed to elucidate the role of geographically important amino acids and evolutionarily conserved long-range interactions …

A Broadly Distributed, Novel Class Of Diiron Enzymes Involved In Para-Aminobenzoate Synthesis, Joseph M. Zambelas

Senior Theses

The overall structure and ligand arrangement of diiron enzymes influence their function and catalytic potential, allowing for them to catalyze an expansive breadth of high energy transformations. The diiron enzyme CADD from Chlamydia trachomatis is involved in a novel biosynthetic pathway for p-aminobenzoic acid (pABA), a precursor for tetrahydrofolate. The unique ligand structure and reactivity of CADD and homolog NE1434 provide an intriguing means to contrast structure function relationships with other known diiron enzymes that activate dioxygen. In this work, studies of CADD and NE1434 orthologs and comparison to other diiron enzymes reveal several sequence motifs that are likely critical …

Understanding How Human Lipoxygenases Bind Molecular Oxygen And Arachidonic Acid Substrate, Austin Paul Primeaux

Honors Capstones

No abstract provided.

The Effects Of Transgenic Alterations Of Bicarbonate-Utilizing Enzymes In Escherichia Coli On The Activity Of Acetyl-Coa Carboxylase, Aniko Alicia Nowakowski

Honors Capstones

No abstract provided.

Visible-Light Photooxidation In Water By 1o2-Generating Supramolecular Hydrogels, Sankarsan Biswas, Mohit Kumar, Andrew Levine, Ian Jimenez, Rein V. Ulijn, Adam Braunschweig

Advanced Science Research Center

We report supramolecular photocatalytic hydrogels, produced by the enzymatically driven self-assembly of low molecular weight gelators (LMWGs). These LMWG precursors are composed of the organic chromophore diketopyrrolopyrrole (DPP), which is bi-functionalized with a series of amino acid (Phe, Tyr, Leu) methyl esters. In situ enzymatic hydrolysis of these photoactive precursors results in supramolecular hydrogels that provide a high density of photocatalytic sites. Under visible light irradiation these hydrophobic fibers recruit the reaction substrates and also produce ¹O₂, which is used here for the photooxidation of thioanisole (aromatic substrate) and cyclohexyl methyl sulfide (aliphatic substrate), with yields as …