Biochemistry, Biophysics, and Structural Biology Commons^™

Genome Announcement For E Cluster Phage Tarkin, Katherine Cleary

Chemistry & Biochemistry Student Scholarship

Katherine Cleary ’23
Major: Biochemistry
Faculty Mentor: Dr. Kathleen Cornely, Chemistry and Biochemistry

Damped Oscillating Phosphoryl Transfer Reaction In The Cyanobacterial Circadian Clock, Hye In Jang, Pyonghwa Kim, Yongick Kim

Chemistry Faculty Research

Most organisms have circadian clocks to ensure the metabolic cycle to resonate with the rhythmic environmental changes without “damping,” or losing robustness. Cyanobacteria is the oldest and simplest form of life that is known to harbor this biological intricacy. Its KaiABC-based central oscillator proteins can be reconstituted inside a test tube, and the post-translational modification cycle occurs with 24 h periodicity. KaiC’s two major phosphorylation sites, Ser-431 and Thr-432, become phosphorylated and dephosphorylated by interacting with KaiA and KaiB, respectively. Here, we mutate Thr-432 into Ser to find the oscillatory phosphoryl transfer reaction damps. Previously, this mutant KaiC was reported …

Purification And Kinetic Characterization Of Mutant R111v Human Cytosolic Malate Dehydrogenase, Jackson Demartino

Chemistry & Biochemistry Student Scholarship

Metabolic profiling for a variety of cancerous cells indicate significant increases in the levels of glucose consumption. To support uncontrolled cell division, cancer cells also present an uncoupling of glycolysis from the citric acid cycle to promote glucose carbons to the synthesis of biomass, therefore, requiring a constant supply of NAD⁺. Recent studies indicate that cancer cells exhibit upregulated cytosolic malate dehydrogenase (MDH1) activity, which catalyzes the conversion of oxaloacetate to malate with the oxidation of NADH, generating NAD⁺. Given its increased activity, MDH1 may serve as a valuable target for treating cancer. Here we report …

Synthesis Of Trifluoromethyl Ketones By (Diethylamino) Sulfur Trifluoride (Dast)-Mediated Nucleophilic Trifluoromethylation Of Benzoic Acids, Michael A. Vescio

Honors College Theses

Within the past few decades, the presence of fluorine containing

organic molecules has increased significantly. Many of the

current industrial production methods are not cost-effective,

practical, or inherently safe. This work describes a new methodology

for the synthesis of trifluoromethyl ketones. Our new method involves

the use of benzoic acid and trifluoromethyl trimethylsilane (TMSCF₃) as starting

materials along with diethylamino sulfur trifluoride (DAST) as a reagent

to obtain moderate to good yields of expected products in a short

reaction times.

Targeting Heat Shock 27 Kda Protein Induces Androgen Receptor Degradation, Yaxin Li

ETD Archive

Glioblastoma (GBM) is the most common and aggressive brain tumor, with very poor prognosis. Androgen receptor (AR) plays a significant role in the progression of GBM, and anti-androgen agents have the potential to be used for the treatment of GBM. However, AR mutation commonly happens in GBM, which makes the anti-androgen agents less effective. Heat shock 27 kDa protein (HSP27) is a well-documented chaperone protein to stabilize AR. Inhibition of HSP27 results in AR degradation regardless the mutation status of AR, which makes HSP27 a good target to abolish AR in GBM. Identified compound I ((N-(3-((2,5-dimethoxybenzyl)oxy)-4-(methylsulfonamido) phenyl)-4-methoxybenzamide) inhibits GBM cell …

Science, Physiology, And Nutrition For The Nonscientist, Judi S. Morrill

Open Educational Resources

A wonderful blend of physiology, nutrition, biochemistry, genetics, biology, evolution, chemistry--what we all need to know as informed citizens. A basic knowledge of the life sciences and how our bodies work--to promote our own good health, especially as we're bombarded with misleading advertisements, soundbites, and the like. DNA fingerprinting, calorie requirements, dietary advice, genetic engineering (including gene editing with CRISPR cas9)--all in an easy-to understand book.

Computational Investigations Into Binding Dynamics Of Tau Protein Antibodies: Using Machine Learning And Biophysical Models To Build A Better Reality, Katherine Lee

University Scholar Projects

Misregulation of post-translational modifications of microtubule-associated protein tau is implicated in several neurodegenerative diseases including Alzheimer’s disease. Hyperphosphorylation of tau promotes aggregation of tau monomers into filaments which are common in tau-associated pathologies. Therefore, tau is a promising target for therapeutics and diagnostics. Recently, high-affinity, high-specificity single-chain variable fragment (scFv) antibodies against pThr-231 tau were generated and the most promising variant (scFv 3.24) displayed 20-fold increased binding affinity to pThr-231 tau compared to the wild-type. The scFv 3.24 variant contained five point mutations, and intriguingly none were in the tau binding site. The increased affinity was hypothesized to occur due …

Exploring Indicator Displacement Assays For Phosphate Detection In Seawater, Francis Radics

Chemistry & Biochemistry Student Scholarship

Francis Radics ’22
Major: Biochemistry
Faculty Mentor: Dr. John Breen, Chemistry and Biochemistry

Indicator displacement assays are based on the optical signal modulation of a noncovalently bound indicator upon dissociation by an analyte species. Our work has focused on exploring the lower detection limits for luminescent displacement assays for inorganic phosphate in seawater using complex ions containing two di(2-picolyl)amine ligands (also called DPA or bis(2-pyridylmethyl)amine), each coordinating a zinc cation. Following the work of B.D. Smith and coworkers, we have prepared three ligands by covalently attaching two DPA moieties, 2,6-bis(chloromethyl) benzene, and 2,6-bis(chloromethyl)-4-methylphenol, and 1,2-phenylenedimethylamine, for assays with 6,7-dihydroxy-4-methanesulfonic acid …

The Discovery And Analysis Of Mycobacteriophage “Rita”, Anna Fakhri

Chemistry & Biochemistry Student Scholarship

Anna Fakhri ’24
Major: Biochemistry
Faculty Mentor: Dr. Kathleen Cornely, Chemistry and Biochemistry

Mycobacteriophage “Rita” was isolated on Mycobacterium smegmatis mc2155 from an enriched soil sample from North Easton, Massachusetts. As Rita infects Mycobacterium smegmatis, further study of the phage was completed in order to determine its ability to be utilized in phage therapy for infections caused by pathogenic Mycobacterium, such as Mycobacterium tuberculosis and Mycobacterium abscessus. Once isolated, the phage DNA was analyzed through PCR to determine the phage belonged to cluster F and subcluster F1. The phage DNA was sequenced, and a genome annotation was completed. The annotation …

Development And Kinetic Survey Of A G148t Mutant Human Cytosolic Malate Dehydrogenase Isoform 3 Enzyme With Oxaloacetate And A-Ketoglutarate, Ethan N. Dionne

Chemistry & Biochemistry Student Scholarship

Cancer cells often use an altered metabolic pathway in which glycolysis, uncoupled from the citric acid cycle, serves as the primary source of ATP. To support cancer cell proliferation and growth, the glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH) must have a constant source of NAD. While lactate dehydrogenase (LDH) in its conversion of pyruvate to lactate is a well-known source of cytosolic NAD for GAPDH activity, cytosolic malate dehydrogenase (MDH1) also plays a role in cell proliferation through its generation of cytosolic NAD by the conversion of OAA to malate. This development has implicated MDH1 in cancer cell metabolism and characterizing …

Proline To Serine Mutation In The Active Site Loop Of Malate Dehydrogenase Alters Substrate Specificity, Olivia J. Schmitt

Chemistry & Biochemistry Student Scholarship

Cancer cells preferentially undergo glycolysis in aerobic environments, a phenomenon termed the Warburg effect. Malate dehydrogenase (MDH) catalyzes the reversible interconversion of malate and oxaloacetate. Human cytosolic malate dehydrogenase (hMDH1) isoform 3 is involved in the malate-aspartate shuttle (MAS), which oxidizes cytosolic NADH. hMDH1 is implicated in high aerobic glycolysis in cancer cells because NAD is a necessary cofactor for glycolysis. Thus, hMDH1 is a promising molecular target for cancer treatment. A single proline residue at position 110 in the mobile active site loop of hMDH1 was mutated to a serine with the intention of altering the enzyme’s substrate specificity. …

Protocol For Fabricating Electroless Nickel Immersion Gold Strain Sensors On Nitrile Butadiene Rubber Gloves For Wearable Electronics, Sara S. Mechael, Yunyun Wu, Yiting Chen, Tricia Breen Carmichael

Chemistry and Biochemistry Publications

This protocol describes the fabrication of patterned conductive gold films on nitrile butadiene rubber (NBR) gloves for wearable strain sensors using electroless nickel immersion gold (ENIG) plating, a solution-based metallization technique. The resulting NBR/ENIG films are strain sensitive; resistance measurements of a patterned sensing array can be used to map human hand motions. This protocol also describes challenges related to the ENIG process and troubleshooting steps to achieve conformal gold films for strain sensing over a large working range. For complete details on the use and execution of this protocol, please refer to Mechael et al. (2021).

Initial Characterization Of Prna From Burkholderia Ambifaria: Developing An Nadph-Dependent Activity Assay For Tryptophan Halogenation, Mahmuda Akter

Theses and Dissertations

Some bacteria produce a potent antifungal agent (pyrrolnitrin) from tryptophan using four dioxygen dependent steps to outcompete other microbes. Each step of this process is catalyzed by an oxygenase encoded by the prnABCD cassette. The first enzymatic step in pyrrolnitrin biosynthesis is the regioselective chlorination of tryptophan to form 7-chlorotryptophan. This halogenation is catalyzed by PrnA, a Flavin dependent oxygenase, which has been isolated and characterized from P. fluorescens. The pyrrolnitrin biosynthesis pathway (prnABCD) has been also observed in the Burkholderia genus. This thesis comprises my studies on the expression, purification, and characterization of PrnA from Burkholderia ambifaria. Beyond the …

Bioactive Recombinant Human Oncostatin M For Nmr-Based Screening In Drug Discovery, Olga A. Mass, Joseph Tuccinardi, Luke Woodbury, Cody L. Wolf, Bri Grantham, Kelsey Holdaway, Xinzhu Pu, Matthew D. King, Don L. Warner, Cheryl L. Jorcyk, Lisa R. Warner

Biomolecular Research Center Publications and Presentations

Oncostatin M (OSM) is a pleiotropic, interleukin-6 family inflammatory cytokine that plays an important role in inflammatory diseases, including inflammatory bowel disease, rheumatoid arthritis, and cancer progression and metastasis. Recently, elevated OSM levels have been found in the serum of COVID-19 patients in intensive care units. Multiple anti-OSM therapeutics have been investigated, but to date no OSM small molecule inhibitors are clinically available. To pursue a high-throughput screening and structure-based drug discovery strategy to design a small molecule inhibitor of OSM, milligram quantities of highly pure, bioactive OSM are required. Here, we developed a reliable protocol to produce highly pure …

Application Of Artificial Intelligence And Machine Learning In Chemistry, Niraj Verma

Chemistry Theses and Dissertations

In the last four years, I have been exposed to various topics in scientific research under the supervision of Dr. Kraka in the CATCO group. Numerous involved chemistry projects were undertaken to gain an understanding of the basic laws of nature involving vibrational spectroscopy, molecular acidity, and catalysts based on transition metals for halogen chemistry. The insights from computational chemistry were then applied to model and predict various complicated problems in chemistry via artificial intelligence. With the help of classical artificial intelligence, the non-covalent interactions governing the properties of proteins and water properties were analyzed. Significant improvements were made in …

Anatomy And Physiology Preparatory Course Textbook (2nd Edition), Carlos Liachovitzky

Open Educational Resources

The goal of this preparatory textbook is to give students a chance to become familiar with some terms and some basic concepts they will find later on in the Anatomy and Physiology course, especially during the first few weeks of the course.

Organization and functioning of the human organism are generally presented starting from the simplest building blocks, and then moving into levels of increasing complexity. This textbook follows the same presentation. It begins introducing the concept of homeostasis, then covers the chemical level, and later on a basic introduction to cellular level, organ level, and organ system level. This …

Ahr Expression On Rorc-Expressing Immune Cells Is Essential For I3c-Mediated Protection Against Colitis, Michal C. Williams

Senior Theses

Colitis is an inflammatory bowel disorder (IBD) whose etiology is attributed to modification in the luminal microbiota and dysregulation in the immune response. Indole is a signaling molecule which is naturally produced by gut luminal microbiota. Indole-3- carbinol (I3C) is a compound commonly found in vegetables and a ligand for the aryl hydrocarbon receptor (AhR). Previous studies have detected decreased expression and activation on the AhR receptor in colitis patients, thought to possibly alter gut microbiota metabolism, subsequently promoting colitis. 1 AhR, expressed in a variety of immune and epithelial cells, contributes to gut homeostasis by affecting vital mediators such …

The Impact Of Natural Rubber As A Toughening Agent On The Strength, Degradability, And Toxicity Of An Algae-Based Bioplastic, Megan Driscoll

Honors College

With the growing attention on widespread plastic usage and its impact on the environment and human health, the need for sustainable alternatives to petroleum-based plastics is more important than ever. One of the most promising solutions is bioplastics; however, current bioplastics struggle to compete with the material properties of petroleum- based plastics. Agar is a sustainable algae-derived hydrocolloid polysaccharide that can be used for bioplastics and biofilms. Despite promising characteristics, bioplastics made from agar are brittle. Common additives, such as the plasticizer glycerol, offset brittleness but sacrifice strength in return. This study looks at the impact of natural rubber as …

Computational Modeling, Energy State Calculations, And Determination Of The Barriers To Rotation Of Atropisomeric Β-Carbolines, Lorenzo Battistoni

Chemistry & Biochemistry Student Scholarship

Major: Biochemistry
Faculty Mentor: Dr. Seann Mulcahy

Axially chiral molecules that have high barriers to rotation about a single bond are called atropisomers. This project aims to expand information on atropisomeric β-carbolines by utilizing computational chemistry to generate energy profiles and determine the barriers to rotation of a library of atropisomeric β-carboline compounds using the program Spartan. Various substituents on the atropisomeric β-carboline scaffold can impact steric strain, electronic effects, and intramolecular hydrogen bonding in the molecule. These factors can impede bond rotation. We will be able to determine which atropisomeric β-carbolines are the best suited to synthesize experimentally using …

An Investigation Of K2 Mycobacteriophage Lysin A Proteins, Ethan Dionne

Chemistry & Biochemistry Student Scholarship

Major: Biochemistry
Faculty Mentor: Dr. Kathleen Cornely, Chemistry and Biochemistry

Indolizine Donor-Based Dyes For Applications In Fluorescence Biological Imaging, William Meador

Honors Theses

NIR emissive fluorophores are intensely researched due to their potential to replace modern imaging procedures. Many molecular strategies have been employed in the literature to optimize fluorophores for deeper NIR absorption and emission, biocompatibility, and higher fluorescence quantum yields. Amongst the fluorophores studied to date, proaromatic indolizine donors are attractive alternatives to traditional alkyl amine and indoline based donors due to their 1) lower energy absorption and emission facilitated by proaromaticity, 2) large Stokes shifts due to increased dihedral angles about the π-system, 3) ease of functionalization and capacity for bioconjugation at the phenyl ring, and 4) potential for further …

Probing Large Intrinsically Disordered Regions Through Novel Sortase-Mediated Ligation, Leah Kjormoe

Scholars Week

In the realm of proteins, it is widely accepted that structure informs function. However, there are many proteins that contain intrinsically disordered regions (IDRs). These regions are areas in which the protein lacks defined structure, and IDPs are also often unstable, which complicates structural studies. NMR spectroscopy is an established method for probing protein structure and has been applied to that end in small IDRs. However, larger IDRs often have spectral overlap that makes data difficult to interpret. Furthermore, low-concentration samples limit spectral clarity. One method to address these difficulties is to use sortase ligation and segmental labeling, which increases …

Surface Mutations Promote Metal Ion Affinity In Haemophilus Influenzae Carbonic Anhydrase, Ella Sheehan

Chemistry & Biochemistry Student Scholarship

Major: Biochemistry
Faculty Mentor: Dr. Kathleen Cornely, Chemistry and Biochemistry

αβ-Carbonic anhydrases are metalloenzymes that are essential to the growth of bacteria, making them a target for antibiotic research in the drug industry. These enzymes contain zinc ions that catalyze the hydration of carbon dioxide to bicarbonate for homeostatic balance. To enhance isolation, surface mutations were completed to introduce histidine residues because they demonstrate affinity for Ni-NTA resin in a column chromatography procedure. After generation and isolation of these mutants, the mutant HICA proteins can be used in a kinetic assay to observe the effect of mutation on the rate …

Towards The Development Of Low-Cost And Easily-Deployable Sensing Platforms For Phosphate, Maureen Pontarelli, Thomas Koch

Chemistry & Biochemistry Student Scholarship

Maureen Pontarelli ’20
Major: Chemistry

Thomas Koch '20
Major: Biochemistry

Faculty Mentor: Dr. John Breen, Chemistry and Biochemistry

Exploration Of K2 Mycobacteriophages With Bred​, Colby Agostino, Olivia Schmitt

Chemistry & Biochemistry Student Scholarship

Colby Agostino ’22
Major: Biochemistry and Computer Science

Olivia Schmitt ’22
Major: Biochemistry

Faculty Mentor: Dr. Kathleen A. Cornely, Chemistry and Biochemistry

ZoeJ and Marcoliusprime are mycobacteriophage capable of infecting tuberculosis causing bacteria via the lytic and lysogenic cycles. The lytic cycle is the form of viral replication that results in cell death. Lysogeny involves phage DNA being integrated with the DNA of the host cell and preserved through binary fission. However, the bacteria causing tuberculosis do not die in the lysogenic phase. This research project will involve creating mutants of ZoeJ and Marcoliusprime that will not contain the genes …

Mycobacteriophage Morphology As A Diagnostic For Cluster Assignment, Ethan Dionne

Chemistry & Biochemistry Student Scholarship

Major: Biochemistry

Faculty Mentor: Dr. Kathleen A. Cornely, Chemistry and Biochemistry

Phages are viral bodies that infect bacterial hosts, and have shown promising applications as alternatives to antibiotics for the treatment of bacterial infections. This project examines the morphology of siphoviridae mycobacteriophage, which have long, flexible, non-contractile tails as well as the characteristic head, called a capsid. Using electron microscopy photos of sequenced phages, tail length and capsid diameter were measured and compared to further characterize morphological relationships between genetically distinct phages. The data presented has the potential to work as a diagnostic tool to classify unsequenced phages to genetically …

Development Of New Methodology Towards Accessing 2-Imidazoline Scaffolds For Combatting Tuberculosis And Multiple Myeloma By Proteasome Modulation, Karen Saldarriaga, Victoria Rasmussen

Chemistry & Biochemistry Student Scholarship

Karen Saldarriaga ’20
Major: Biochemistry

Victoria Rasmussen '20
Major: Biology and Psychology

Faculty Mentor: Dr. Travis K. Bethel, Chemistry and Biochemistry

Multiple Myeloma (MM) is a disorder of differentiated B cells in which the inhibition of the proteasome is standard care. The current drug, bortezomib, used to treat MM is ineffective against drug tolerance where 97% of all patients become intolerant within a few years. Imidazoline scaffolds are capable of overcoming that resistance and delaying MM tumor growth. We believe we will be able to effectively yield imidazolines. Synthesis will occur with commercially available starting materials, making the process less …

Periodic Table Club, Makayla Gill, Kailynn Jensen

Honors 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.

Comparative Analysis Of The Human Serine Hydrolase Ovca2 To The Model Serine Hydrolase Homolog Fsh1 From S. Cerevisiae, Jessica S. Bun, Michael D. Slack, Daniel E. Schemenauer, R. Jeremy Johnson

Scholarship and Professional Work - LAS

Over 100 metabolic serine hydrolases are present in humans with confirmed functions in metabolism, immune response, and neurotransmission. Among potentially clinically relevant but uncharacterized human serine hydrolases is OVCA2, a serine hydrolase that has been linked with a variety of cancer-related processes. Herein, we developed a heterologous expression system for OVCA2 and determined the comprehensive substrate specificity of OVCA2 against two ester substrate libraries. Based on this analysis, OVCA2 was confirmed as a serine hydrolase with a strong preference for long-chain alkyl ester substrates (>10-carbons) and high selectivity against a variety of short, branched, and substituted esters. Substitutional analysis …

10th Annual Postdoctoral Science Symposium, University Of Texas Md Anderson Cancer Center Postdoctoral Association

Annual Postdoctoral Science Symposium Abstracts

The Annual Postdoctoral Science Symposium (APSS) was initiated on August 4, 2011, by the MD Anderson Postdoctoral Association to provide a platform for talented postdoctoral fellows throughout the Texas Medical Center to present their work to a wider audience.

APSS is a scientific symposium organized by postdoctoral fellows from The University of Texas MD Anderson Cancer Center that welcomes submissions and presentations from postdoctoral fellows from all Texas Medical Center affiliated institutions and other Houston area institutions. The APSS provides a professional venue for postdoctoral scientists to develop, clarify and refine their research as result of formal reviews and critiques …