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Full-Text Articles in Other Biochemistry, Biophysics, and Structural Biology

Oligogalactolipid Production During Cold Challenge Is Conserved In Early Diverging Lineages, Allison C. Barnes, Jennifer L. Myers, Samantha M. Surber, Zhikai Liang, Jeffrey P. Mower, James Schnable, Rebecca Roston Jan 2023

Oligogalactolipid Production During Cold Challenge Is Conserved In Early Diverging Lineages, Allison C. Barnes, Jennifer L. Myers, Samantha M. Surber, Zhikai Liang, Jeffrey P. Mower, James Schnable, Rebecca Roston

Department of Biochemistry: Faculty Publications

Oligogalactolipid production is a response to severe cold in many land plant lineages. It occurs during times of membrane damage and can be reproduced in multiple species by cytosolic acidification.

Severe cold, defined as a damaging cold beyond acclimation temperatures, has unique responses, but the signaling and evolution of these responses are not well understood. Production of oligogalactolipids, which is triggered by cytosolic acidification in Arabidopsis (Arabidopsis thaliana), contributes to survival in severe cold. Here, we investigated oligogalactolipid production in species from bryophytes to angiosperms. Production of oligogalactolipids differed within each clade, suggesting multiple evolutionary origins of severe …


Factors Influencing Instructors’ Adoption And Continued Use Of Computing Science Technologies: A Case Study In The Context Of Cell Collective, Changsoo Song, Resa M. Helikar, Wendy M. Smith, Tomáš Helikar Jan 2023

Factors Influencing Instructors’ Adoption And Continued Use Of Computing Science Technologies: A Case Study In The Context Of Cell Collective, Changsoo Song, Resa M. Helikar, Wendy M. Smith, Tomáš Helikar

Department of Biochemistry: Faculty Publications

Acquiring computational modeling and simulation skills has become ever more critical for students in life sciences courses at the secondary and tertiary levels. Many modeling and simulation tools have been created to help instructors nurture those skills in their classrooms. Understanding the factors that may motivate instructors to use such tools is crucial to improve students’ learning, especially for having authentic modeling and simulation learning experiences. This study designed and tested a decomposed technology acceptance model in which the perceived usefulness and perceived ease of use constructs are split between the teaching and learning sides of the technology to examine …


Conformal Electrodeposition Of Antimicrobial Hydrogels Formed By Self-Assembled Peptide Amphiphiles, Gervasio Zaldivar, Jiachen Feng, Leonardo Lizarraga, Yafan Yu, Luana De Campos, Kelly Mari Pires De Oliveira, Kurt Piepenbrink, Martin Conda-Sheridan, Mario Tagliazucchi Jan 2023

Conformal Electrodeposition Of Antimicrobial Hydrogels Formed By Self-Assembled Peptide Amphiphiles, Gervasio Zaldivar, Jiachen Feng, Leonardo Lizarraga, Yafan Yu, Luana De Campos, Kelly Mari Pires De Oliveira, Kurt Piepenbrink, Martin Conda-Sheridan, Mario Tagliazucchi

Department of Biochemistry: Faculty Publications

The colonization of biomedical surfaces by bacterial biofilms is concerning because these microorganisms display higher antimicrobial resistance in biofilms than in liquid cultures. Developing antimicrobial coatings that can be easily applied to medically-relevant complex-shaped objects, such as implants and surgical instruments, is an important and challenging research direction. This work reports the preparation of antibacterial surfaces via the electrodeposition of a conformal hydrogel of self-assembling cationic peptide-amphiphiles (PAs). Hydrogels of three PAs are electrodeposited: C16K2, C16K3, and C18K2, where Cn is an alkyl chain of n methylene …


The Effects Of Exogenously Applied Antioxidants On Plant Growth And Resilience, Aline Rodrigues De Queiroz, Connor Hines, Jeremy Brown, Seema Sahay, Jithesh Vijayan, Julie M. Stone, Nate Bickford, Melissa Wuellner, Katarzyna Glowacka, Nicole R. Buan, Rebecca Roston Jan 2023

The Effects Of Exogenously Applied Antioxidants On Plant Growth And Resilience, Aline Rodrigues De Queiroz, Connor Hines, Jeremy Brown, Seema Sahay, Jithesh Vijayan, Julie M. Stone, Nate Bickford, Melissa Wuellner, Katarzyna Glowacka, Nicole R. Buan, Rebecca Roston

Department of Biochemistry: Faculty Publications

Plant growth and resilience require balancing an inherently oxidative metabolism with powerful antioxidant systems that help maintain homeostasis. When the environment changes, reactive oxygen species are potent indicators of that change, allowing adaptation through re-balancing metabolism and antioxidant systems. A large body of evidence supports the use of exogenously applied antioxidants to improve both plant growth and their resilience to stress. Notably, some phenotypic effects are similar upon the application of chemically diverse antioxidants, while others are distinct. In this review, we analyze research from antioxidant treatment experiments and highlight the similarities in their practical applications and their effects on …


Genome-Wide Investigation Of Snrk2 Gene Family In Two Jute Species: Corchorus Olitorius And Corchorus Capsularis, Borhan Ahmed, Fakhrul Hasan, Anika Tabassum, Rasel Ahmed, Rajnee Hassan, Ruhul Amin, Mobashwer Alam Jan 2023

Genome-Wide Investigation Of Snrk2 Gene Family In Two Jute Species: Corchorus Olitorius And Corchorus Capsularis, Borhan Ahmed, Fakhrul Hasan, Anika Tabassum, Rasel Ahmed, Rajnee Hassan, Ruhul Amin, Mobashwer Alam

Department of Biochemistry: Faculty Publications

Background Sucrose non-fermenting-1 (SNF1)-related protein kinase 2 (SnRK2), a plant-specifc serine/threonine kinase family, is associated with metabolic responses, including abscisic acid signaling under biotic and abiotic stresses. So far, no information on a genome-wide investigation and stress-mediated expression profling of jute SnRK2 is available. Recent whole-genome sequencing of two Corchorus species prompted to identify and characterize this SnRK2 gene family.

Result We identifed seven SnRK2 genes of each of Corchorus olitorius (Co) and C. capsularis (Cc) genomes, with similar physico-molecular properties and sub-group patterns of other models and related crops. In both species, the SnRK2 gene …


Advancements In Computational Modelling Of Biological Systems: Seventh Annual Sysmod Meeting, Bhanwar Lal Puniya, Andreas Dräger Jan 2023

Advancements In Computational Modelling Of Biological Systems: Seventh Annual Sysmod Meeting, Bhanwar Lal Puniya, Andreas Dräger

Department of Biochemistry: Faculty Publications

The Computational Modelling of Systems Biology (SysMod) Community of Special Interest (COSI) convenes annually at the Intelligent Systems for Molecular Biology (ISMB) conference to facilitate knowledge dissemination and exchange of research findings on systems modelling from interdisciplinary domains. The SysMod meeting 2022 was held in a hybrid mode in Madison, Wisconsin, spanning a 1-day duration centred on modelling techniques, applications, and single-cell technology implementations. The meeting showcased innovative approaches to modelling biological systems using cell-specific and multiscale modelling, multiomics data integration, and novel tools to develop systems models using single-cell and multiomics technology. The meeting also recognized outstanding research by …


Structural Basis Of Dna Binding By The Whib-Like Transcription Factor Whib3 In Mycobacterium Tuberculosis, Tao Wan, Magdaléna Horová, Vimmy Khetrapal, Shanren Li, Camden Jones, Andrew Schacht, Xinghui Sun, Limei Zhang Jan 2023

Structural Basis Of Dna Binding By The Whib-Like Transcription Factor Whib3 In Mycobacterium Tuberculosis, Tao Wan, Magdaléna Horová, Vimmy Khetrapal, Shanren Li, Camden Jones, Andrew Schacht, Xinghui Sun, Limei Zhang

Department of Biochemistry: Faculty Publications

Mycobacterium tuberculosis (Mtb) WhiB3 is an iron–sulfur cluster-containing transcription factor belonging to a subclass of the WhiB-Like (Wbl) family that is widely distributed in the phylum Actinobacteria. WhiB3 plays a crucial role in the survival and pathogenesis of Mtb. It binds to the conserved region 4 of the principal sigma factor (σA4) in the RNA polymerase holoenzyme to regulate gene expression like other known Wbl proteins in Mtb. However, the structural basis of how WhiB3 coordinates with σA4 to bind DNA and regulate transcription is unclear. Here we determined crystal structures …


Akkermansia Muciniphila And Its Membrane Protein Ameliorates Intestinal Inflammatory Stress And Promotes Epithelial Wound Healing Via Crebh And Mir‑143/145, Henry Wade, Kaichao Pan, Qihua Duan, Szczepan Kaluzny, Ekta Pandey, Linda Fatumoju, Viswanathan Saraswathi, Rongxue Wu, Edward N. Harris, Qiaozhu Su Jan 2023

Akkermansia Muciniphila And Its Membrane Protein Ameliorates Intestinal Inflammatory Stress And Promotes Epithelial Wound Healing Via Crebh And Mir‑143/145, Henry Wade, Kaichao Pan, Qihua Duan, Szczepan Kaluzny, Ekta Pandey, Linda Fatumoju, Viswanathan Saraswathi, Rongxue Wu, Edward N. Harris, Qiaozhu Su

Department of Biochemistry: Faculty Publications

Background The intestinal epithelial barrier is the interface for interaction between gut microbiota and host metabolic systems. Akkermansia muciniphila (A. muciniphila) is a key player in the colonic microbiota that resides in the mucus layer, whose abundance is selectively decreased in the faecal microbiota of inflammatory bowel disease (IBD) patients. This study aims to investigate the regulatory mechanism among A. muciniphila, a transcription factor cAMPresponsive element-binding protein H (CREBH), and microRNA-143/145 (miR-143/145) in intestinal inflammatory stress, gut barrier integrity and epithelial regeneration.

Methods A novel mouse model with increased colonization of A muciniphila in the intestine of CREBH knockout …


Hiv-Tat Exacerbates The Actions Of Atazanavir, Efavirenz, And Ritonavir On Cardiac Ryanodine Receptor (Ryr2), Imam Abdulrahman Bin Faisal University, Chengju Tian, Sean R. Bidasee, Zachary L. Venn, Evan Schroder, Nick Y. Palermo, Mohammad Alshabeeb, Benson J. Edagwa, Jason J. Payne, Keshoer R. Bidasee Dec 2022

Hiv-Tat Exacerbates The Actions Of Atazanavir, Efavirenz, And Ritonavir On Cardiac Ryanodine Receptor (Ryr2), Imam Abdulrahman Bin Faisal University, Chengju Tian, Sean R. Bidasee, Zachary L. Venn, Evan Schroder, Nick Y. Palermo, Mohammad Alshabeeb, Benson J. Edagwa, Jason J. Payne, Keshoer R. Bidasee

Department of Biochemistry: Faculty Publications

The incidence of sudden cardiac death (SCD) in people living with HIV infection (PLWH), especially those with inadequate viral suppression, is high and the reasons for this remain incompletely characterized. The timely opening and closing of type 2 ryanodine receptor (RyR2) is critical for ensuring rhythmic cardiac contraction–relaxation cycles, and the disruption of these processes can elicit Ca2+ waves, ventricular arrhythmias, and SCD. Herein, we show that the HIV protein Tat (HIVTat: 0–52 ng/mL) and therapeutic levels of the antiretroviral drugs atazanavir (ATV: 0–25,344 ng/mL), efavirenz (EFV: 0–11,376 ng/mL), and ritonavir (RTV: 0–25,956 ng/mL) bind to and modulate the …


Therapies For Mitochondrial Disorders, Kayli Sousa Smyth, Anne Mulvihill Dec 2022

Therapies For Mitochondrial Disorders, Kayli Sousa Smyth, Anne Mulvihill

SURE Journal: Science Undergraduate Research Experience Journal

Mitochondria are cytoplasmic, double-membrane organelles that synthesise adenosine triphosphate (ATP). Mitochondria contain their own genome, mitochondrial DNA (mtDNA), which is maternally inherited from the oocyte. Mitochondrial proteins are encoded by either nuclear DNA (nDNA) or mtDNA, and both code for proteins forming the mitochondrial oxidative phosphorylation (OXPHOS) complexes of the respiratory chain. These complexes form a chain that allows the passage of electrons down the electron transport chain (ETC) through a proton motive force, creating ATP from adenosine diphosphate (ADP). This study aims to explore current and prospective therapies for mitochondrial disorders (MTDS). MTDS are clinical syndromes coupled with abnormalities …


Arginine Methylation Of The Pgc-1Α C‑Terminus Is Temperature- Dependent, Meryl Mendoz, Mariel Mendoza, Tiffany Lubrino, Sidney Briski, Immaculeta Osuji, Janielle Cuala, Brendan Ly, Ivan Ocegueda, Harvey Peralta, Benjamin A. Garcia, Cecilia Zurita-Lopez Dec 2022

Arginine Methylation Of The Pgc-1Α C‑Terminus Is Temperature- Dependent, Meryl Mendoz, Mariel Mendoza, Tiffany Lubrino, Sidney Briski, Immaculeta Osuji, Janielle Cuala, Brendan Ly, Ivan Ocegueda, Harvey Peralta, Benjamin A. Garcia, Cecilia Zurita-Lopez

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

We set out to determine whether the C-terminus (amino acids 481–798) of peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α, UniProt Q9UBK2), a regulatory metabolic protein involved in mitochondrial biogenesis, and respiration, is an arginine methyltransferase substrate. Arginine methylation by protein arginine methyltransferases (PRMTs) alters protein function and thus contributes to various cellular processes. In addition to confirming methylation of the C-terminus by PRMT1 as described in the literature, we have identified methylation by another member of the PRMT family, PRMT7. We performed in vitro methylation reactions using recombinant mammalian PRMT7 and PRMT1 at 37, 30, 21, 18, and 4 °C. …


Quantum Computations And Molecular Dynamics Simulations: From The Fundamentals Of Antimicrobial Resistance To Neurological Diseases, Angel Tamez Dec 2022

Quantum Computations And Molecular Dynamics Simulations: From The Fundamentals Of Antimicrobial Resistance To Neurological Diseases, Angel Tamez

Electronic Theses and Dissertations

Biophysical phenomena are modeled using a combination of quantum and classical methods to interpret and supplement three distinct and diverse problems in this dissertation. In the first project, decarboxylation reactions are ubiquitous across chemical and biological disciplines, yet the origin of non-catalytic solvent effects remains elusive. Specific solvent structure and energetics have not been well described for the monoanion of malonate, nor corrected from the gas-phase charge-assisted intramolecular hydrogen bond model known as “pseudochair”. In the aqueous phase, a low-lying energy conformer known as the “orthogonal conformation” is computed to be preferred by a three-water cluster of hydrogen bonding over …


Insights Into The Biotechnology Potential Of Methanosarcina, Sean Carr, Nicole R. Buan Dec 2022

Insights Into The Biotechnology Potential Of Methanosarcina, Sean Carr, Nicole R. Buan

Department of Biochemistry: Faculty Publications

Methanogens are anaerobic archaea which conserve energy by producing methane. Found in nearly every anaerobic environment on earth, methanogens serve important roles in ecology as key organisms of the global carbon cycle, and in industry as a source of renewable biofuels. Environmentally, methanogenic archaea play an essential role in the reintroducing unavailable carbon to the carbon cycle by anaerobically converting low-energy, terminal metabolic degradation products such as one and two-carbon molecules into methane which then returns to the aerobic portion of the carbon cycle. In industry, methanogens are commonly used as an inexpensive source of renewable biofuels as well as …


A Novel Transmembrane Ligand Inhibits T Cell Receptor Activation, Yujie Ye Dec 2022

A Novel Transmembrane Ligand Inhibits T Cell Receptor Activation, Yujie Ye

Doctoral Dissertations

T lymphocytes (T cells) play essential roles in the adaptive immune system. Each mature T cell expresses one type of functional T cell receptor (TCR). The TCR recognizes antigens bound to the major histocompatibility complex (MHC) in antigen presenting cells. The resulting stimulation signal crosses the transmembrane domain of TCR and initiates downstream signaling cascades. The human immune system relies on TCRs to recognize a variety of pathogens. Normally, TCR can distinguish the self-antigens from pathogenic antigens. However, dysfunction or aberrant expression of TCRs causes different inflammatory and autoimmune diseases, which afflict millions of people annually (Chapter I). Current treatments …


A Review Of Radiation-Induced Alterations Of Multi-Omic Profiles, Radiation Injury Biomarkers, And Countermeasures, Sushil K. Shakyawar, Nitish K. Mishra, Neetha N. Vellichirammal, Lynnette Cary, Tomáš Helikar, Robert Powers, Rebecca E. Oberley-Deegan, David B. Berkowitz, Kenneth W. Bayles, Vijay K. Singh, Chittibabu Guda Nov 2022

A Review Of Radiation-Induced Alterations Of Multi-Omic Profiles, Radiation Injury Biomarkers, And Countermeasures, Sushil K. Shakyawar, Nitish K. Mishra, Neetha N. Vellichirammal, Lynnette Cary, Tomáš Helikar, Robert Powers, Rebecca E. Oberley-Deegan, David B. Berkowitz, Kenneth W. Bayles, Vijay K. Singh, Chittibabu Guda

Department of Biochemistry: Faculty Publications

Increasing utilization of nuclear power enhances the risks associated with industrial accidents, occupational hazards, and the threat of nuclear terrorism. Exposure to ionizing radiation interferes with genomic stability and gene expression resulting in the disruption of normal metabolic processes in cells and organs by inducing complex biological responses. Exposure to high-dose radiation causes acute radiation syndrome, which leads to hematopoietic, gastrointestinal, cerebrovascular, and many other organ-specific injuries. Altered genomic variations, gene expression, metabolite concentrations, and microbiota profiles in blood plasma or tissue samples reflect the whole-body radiation injuries. Hence, multi-omic profiles obtained from high-resolution omics platforms offer a holistic approach …


Reproducibility Of Protein X-Ray Diffuse Scattering And Potential Utility For Modeling Atomic Displacement Parameters, Zhen Su, Medhanjali Dasgupta, Frédéric Poitevin, Irimpan I. Mathews, Henry Van Den Bedem, Michael E. Wall, Chun Hong Yoon, Mark A. Wilson Sep 2022

Reproducibility Of Protein X-Ray Diffuse Scattering And Potential Utility For Modeling Atomic Displacement Parameters, Zhen Su, Medhanjali Dasgupta, Frédéric Poitevin, Irimpan I. Mathews, Henry Van Den Bedem, Michael E. Wall, Chun Hong Yoon, Mark A. Wilson

Department of Biochemistry: Faculty Publications

Protein structure and dynamics can be probed using x-ray crystallography. Whereas the Bragg peaks are only sensitive to the average unit-cell electron density, the signal between the Bragg peaks—diffuse scattering—is sensitive to spatial correlations in electron-density variations. Although diffuse scattering contains valuable information about protein dynamics, the diffuse signal is more difficult to isolate from the background compared to the Bragg signal, and the reproducibility of diffuse signal is not yet well understood. We present a systematic study of the reproducibility of diffuse scattering from isocyanide hydratase in three different protein forms. Both replicate diffuse datasets and datasets obtained from …


Editorial: Function And Formation Of Mitochondrial Metalloproteome, Michał Wasilewski, Vishal M. Gohil, Oleh Khalimonchuk Sep 2022

Editorial: Function And Formation Of Mitochondrial Metalloproteome, Michał Wasilewski, Vishal M. Gohil, Oleh Khalimonchuk

Department of Biochemistry: Faculty Publications

No abstract provided.


Loss Of Num1-Mediated Cortical Dynein Anchoring Negatively Impacts Respiratory Growth, Antoineen J. White, Clare S. Harper, Erica M. Rosario, Jonathan V. Dietz, Hannah G. Addis, Jennifer L. Fox, Oleh Khalimonchuk, Laura L. Lackner Sep 2022

Loss Of Num1-Mediated Cortical Dynein Anchoring Negatively Impacts Respiratory Growth, Antoineen J. White, Clare S. Harper, Erica M. Rosario, Jonathan V. Dietz, Hannah G. Addis, Jennifer L. Fox, Oleh Khalimonchuk, Laura L. Lackner

Department of Biochemistry: Faculty Publications

Num1 is a multifunctional protein that both tethers mitochondria to the plasma membrane and anchors dynein to the cell cortex during nuclear inheritance. Previous work has examined the impact loss of Num1-based mitochondrial tethering has on dynein function in Saccharomyces cerevisiae; here, we elucidate its impact on mitochondrial function. We find that like mitochondria, Num1 is regulated by changes in metabolic state, with the protein levels and cortical distribution of Num1 differing between fermentative and respiratory growth conditions. In cells lacking Num1, we observe a reproducible respiratory growth defect, suggesting a role for Num1 in not only maintaining mitochondrial …


Ncoa4 Regulates Iron Recycling And Responds To Hepcidin Activity And Lipopolysaccharide In Macrophages, Cole A. Guggisberg, Juyoung Kim, Jaekwon Lee, Xiaoli Chen, Moon-Suhn Ryu Aug 2022

Ncoa4 Regulates Iron Recycling And Responds To Hepcidin Activity And Lipopolysaccharide In Macrophages, Cole A. Guggisberg, Juyoung Kim, Jaekwon Lee, Xiaoli Chen, Moon-Suhn Ryu

Department of Biochemistry: Faculty Publications

Macrophages, via erythrophagocytosis, recycle iron from effete erythrocytes to newly developing red blood cells. Conversion of potentially cytotoxic levels of iron from its heme into nonheme form during iron recycling is safely accomplished via coordinated regulations of cellular iron transport and homeostasis. Herein, we demonstrate the roles and regulation of NCOA4 (nuclear receptor coactivator 4)-mediated ferritinophagy in macrophages after erythrophagocytosis using the mouse macrophage cell line J774 cells. Ferritin in J774 cells increased with the rise of nonheme iron by erythrocyte ingestion and declined when total cellular iron contents subsequently decreased. NCOA4, a selective autophagic cargo receptor for ferritin, was …


Editorial: Mitochondria, Metabolism And Cardiovascular Diseases, Jun-Ichiro Koga, Xinghui Sun, Masuko Ushio-Fukai Aug 2022

Editorial: Mitochondria, Metabolism And Cardiovascular Diseases, Jun-Ichiro Koga, Xinghui Sun, Masuko Ushio-Fukai

Department of Biochemistry: Faculty Publications

No abstract provided.


Metabolite Damage And Damage Control In A Minimal Genome, Drago Haas, Antje M. Thamm, Jiayi Sun, Lili Huang, Lijie Sun, Guillaume A.W. Beaudoin, Kim S. Wise, Claudia Lerma-Ortiz, Steven D. Bruner, Marian Breuer, Zaida Luthey-Schulten, Jiusheng Lin, Mark A. Wilson, Greg Brown, Alexander F. Yakunin, Inna Kurilyak, Jacob Folz, Oliver Fiehn, John I. Glass, Andrew D. Hanson, Christopher S. Henry, Valérie De Crécy-Lagard Aug 2022

Metabolite Damage And Damage Control In A Minimal Genome, Drago Haas, Antje M. Thamm, Jiayi Sun, Lili Huang, Lijie Sun, Guillaume A.W. Beaudoin, Kim S. Wise, Claudia Lerma-Ortiz, Steven D. Bruner, Marian Breuer, Zaida Luthey-Schulten, Jiusheng Lin, Mark A. Wilson, Greg Brown, Alexander F. Yakunin, Inna Kurilyak, Jacob Folz, Oliver Fiehn, John I. Glass, Andrew D. Hanson, Christopher S. Henry, Valérie De Crécy-Lagard

Department of Biochemistry: Faculty Publications

Analysis of the genes retained in the minimized Mycoplasma JCVI-Syn3A genome established that systems that repair or preempt metabolite damage are essential to life. Several genes known to have such functions were identified and experimentally validated, including 5-formyltetrahydrofolate cycloligase, coenzyme A (CoA) disulfide reductase, and certain hydrolases. Furthermore, we discovered that an enigmatic YqeK hydrolase domain fused to NadD has a novel proofreading function in NAD synthesis and could double as a MutT-like sanitizing enzyme for the nucleotide pool. Finally, we combined metabolomics and cheminformatics approaches to extend the core metabolic map of JCVI-Syn3A to include promiscuous enzymatic reactions and …


Applications Of Nuclear Magnetic Resonance Spectroscopy: From Drug Discovery To Protein Structure And Dynamics., Mark Vincent C. Dela Cerna Aug 2022

Applications Of Nuclear Magnetic Resonance Spectroscopy: From Drug Discovery To Protein Structure And Dynamics., Mark Vincent C. Dela Cerna

Electronic Theses and Dissertations

The versatility of nuclear magnetic resonance (NMR) spectroscopy is apparent when presented with diverse applications to which it can contribute. Here, NMR is used i) as a screening/ validation tool for a drug discovery program targeting the Phosphatase of Regenerating Liver 3 (PRL3), ii) to characterize the conformational heterogeneity of p53 regulator, Murine Double Minute X (MDMX), and iii) to characterize the solution dynamics of guanosine monophosphate kinase (GMPK). Mounting evidence suggesting roles for PRL3 in oncogenesis and metastasis has catapulted it into prominence as a cancer drug target. Yet, despite significant efforts, there are no PRL3 small molecule inhibitors …


Variation On A Theme: The Structures And Biosynthesis Of Specialized Fatty Acid Natural Products In Plants, Samuel Scott, Edgar B. Cahoon, Lucas Busta Jun 2022

Variation On A Theme: The Structures And Biosynthesis Of Specialized Fatty Acid Natural Products In Plants, Samuel Scott, Edgar B. Cahoon, Lucas Busta

Department of Biochemistry: Faculty Publications

Plants are able to construct lineage-specific natural products from a wide array of their core metabolic pathways. Considerable progress has been made toward documenting and understanding, for example, phenylpropanoid natural products derived from phosphoenolpyruvate via the shikimate pathway, terpenoid compounds built using isopentyl pyrophosphate, and alkaloids generated by the extensive modification of amino acids. By comparison, natural products derived from fatty acids have received little attention, except for unusual fatty acids in seed oils and jasmonate-like oxylipins. However, scattered but numerous reports show that plants are able to generate many structurally diverse compounds from fatty acids, including some with highly …


Dj-1 Is Not A Deglycase And Makes A Modest Contribution To Cellular Defense Against Methylglyoxal Damage In Neurons, Melissa Conti Mazza, Sarah C. Shuck, Jiusheng Lin, Michael Moxley, John Termini, Mark R. Cookson, Mark A. Wilson Jun 2022

Dj-1 Is Not A Deglycase And Makes A Modest Contribution To Cellular Defense Against Methylglyoxal Damage In Neurons, Melissa Conti Mazza, Sarah C. Shuck, Jiusheng Lin, Michael Moxley, John Termini, Mark R. Cookson, Mark A. Wilson

Department of Biochemistry: Faculty Publications

Human DJ-1 is a cytoprotective protein whose absence causes Parkinson's disease and is also associated with other diseases. DJ-1 has an established role as a redox-regulated protein that defends against oxidative stress and mitochondrial dysfunction. Multiple studies have suggested that DJ-1 is also a protein/nucleic acid deglycase that plays a key role in the repair of glycation damage caused by methylglyoxal (MG), a reactive α-keto aldehyde formed by central metabolism. Contradictory reports suggest that DJ-1 is a glyoxalase but not a deglycase and does not play a major role in glycation defense. Resolving this issue is important for understanding how …


Altered Collective Mitochondrial Dynamics In The Arabidopsis Msh1 Mutant Compromising Organelle Dna Maintenance, Joanna M. Chustecki, Ross D. Etherington, Daniel J. Gibbs, Iain G. Johnston Jun 2022

Altered Collective Mitochondrial Dynamics In The Arabidopsis Msh1 Mutant Compromising Organelle Dna Maintenance, Joanna M. Chustecki, Ross D. Etherington, Daniel J. Gibbs, Iain G. Johnston

Department of Biochemistry: Faculty Publications

Mitochondria form highly dynamic populations in the cells of plants (and almost all eukaryotes). The characteristics and benefits of this collective behaviour, and how it is influenced by nuclear features, remain to be fully elucidated. Here, we use a recently developed quantitative approach to reveal and analyse the physical and collective ‘social’ dynamics of mitochondria in an Arabidopsis msh1 mutant where the organelle DNA maintenance machinery is compromised. We use a newly created line combining the msh1 mutant with mitochondrially targeted green fluorescent protein (GFP), and characterize mitochondrial dynamics with a combination of single-cell time-lapse microscopy, computational tracking, and network …


In Silico Identification Of Potential Inhibitors Of The Sars‑Cov‑2 Nucleocapsid Through Molecular Docking‑Based Drug Repurposing, Rukhsar Afreen, Saleem Iqbal, Ab Rauf Shah, Heena Afreen, Maitreyi College, Mohd. Shkir May 2022

In Silico Identification Of Potential Inhibitors Of The Sars‑Cov‑2 Nucleocapsid Through Molecular Docking‑Based Drug Repurposing, Rukhsar Afreen, Saleem Iqbal, Ab Rauf Shah, Heena Afreen, Maitreyi College, Mohd. Shkir

Department of Biochemistry: Faculty Publications

SARS-CoV-2 is the virus responsible for the COVID-19 pandemic, and its effects on people worldwide continue to grow. Protein-targeted therapeutics are currently unavailable for this virus. As with other coronaviruses, the nucleocapsid (N) protein is the most conserved RNA-binding structural protein of SARS-CoV-2. The N protein is an appealing target because of its functional role in viral transcription and replication. Therefore, molecular docking method for structure-based drug design was used to investigate the binding energy and binding modes of various anti-N inhibitors in depth. The inhibitors selected were originally developed to target stress granules and other molecules involved in RNA …


Guard-Cell-Targeted Overexpression Of Arabidopsis Hexokinase 1 Can Improve Water Use Efficiency In Field-Grown Tobacco Plants, Liana G. Acevedo-Siaca, Katarzyna Glowacka, Steven M. Driever, Coralie E. Salesse-Smith, Nitsan Lugassi, David Granot, Stephen P. Long, Johannes Kromdijk May 2022

Guard-Cell-Targeted Overexpression Of Arabidopsis Hexokinase 1 Can Improve Water Use Efficiency In Field-Grown Tobacco Plants, Liana G. Acevedo-Siaca, Katarzyna Glowacka, Steven M. Driever, Coralie E. Salesse-Smith, Nitsan Lugassi, David Granot, Stephen P. Long, Johannes Kromdijk

Department of Biochemistry: Faculty Publications

Water deficit currently acts as one of the largest limiting factors for agricultural productivity worldwide. Additionally, limitation by water scarcity is projected to continue in the future with the further onset of effects of global climate change. As a result, it is critical to develop or breed for crops that have increased water use efficiency and that are more capable of coping with water scarce conditions. However, increased intrinsic water use efficiency (iWUE) typically brings a trade-off with CO2 assimilation as all gas exchange is mediated by stomata, through which CO2 enters the leaf while water vapor exits. …


Evaluation Of Current Methods To Detect Cellular Leucine-Rich Repeat Kinase 2 (Lrrk2) Kinase Activity, Belén Fernández, Vinita G. Chittoor-Vinod, Jillian H. Kluss, Kaela Kelly, Nicole Bryant, An Phu Tran Nguyen, Syed A. Bukhari, Nathan J. Smith, Antonio Jesús Lara Ordóñez, Elena Fdez, Marie-Christine Chartier-Harlin, Thomas J. Montine, Mark A. Wilson, Darren J. Moore, Andrew B. West, Mark R. Cookson, R. Jeremy Nichols, Sabine Hilfiker May 2022

Evaluation Of Current Methods To Detect Cellular Leucine-Rich Repeat Kinase 2 (Lrrk2) Kinase Activity, Belén Fernández, Vinita G. Chittoor-Vinod, Jillian H. Kluss, Kaela Kelly, Nicole Bryant, An Phu Tran Nguyen, Syed A. Bukhari, Nathan J. Smith, Antonio Jesús Lara Ordóñez, Elena Fdez, Marie-Christine Chartier-Harlin, Thomas J. Montine, Mark A. Wilson, Darren J. Moore, Andrew B. West, Mark R. Cookson, R. Jeremy Nichols, Sabine Hilfiker

Department of Biochemistry: Faculty Publications

Background: Coding variation in the Leucine rich repeat kinase 2 gene linked to Parkinson’s disease (PD) promotes enhanced activity of the encoded LRRK2 kinase, particularly with respect to autophosphorylation at S1292 and/or phosphorylation of the heterologous substrate RAB10.

Objective: To determine the inter-laboratory reliability of measurements of cellular LRRK2 kinase activity in the context of wildtype or mutant LRRK2 expression using published protocols.

Methods: Benchmark western blot assessments of phospho-LRRK2 and phospho-RAB10 were performed in parallel with in situ immunological approaches in HEK293T, mouse embryonic fibroblasts, and lymphoblastoid cell lines. Rat brain tissue, with or without adenovirus-mediated …


Investigation Of The Binding Domain Interfaces Of The C-Terminus Of The Albino3 Insertase And The 43kda Chloroplast Signal Recognition Particle Subunit Via Single Molecule Förster Resonance Energy Transfer, Amanda Tomanek May 2022

Investigation Of The Binding Domain Interfaces Of The C-Terminus Of The Albino3 Insertase And The 43kda Chloroplast Signal Recognition Particle Subunit Via Single Molecule Förster Resonance Energy Transfer, Amanda Tomanek

Chemistry & Biochemistry Undergraduate Honors Theses

Fluorescent labeling is a technique used for visualizing functional groups contained in biomolecules by fluorescence imaging. This technique was used in this project to analyze post-translational targeting of light-harvesting chlorophyll-binding proteins (LHCP), which are the core complexes that harvest sunlight to drive photosynthetic electron transfer. This protein is synthesized in the cytosol and post-translationally targeted to the stroma of chloroplasts. CpSRP43 is a signal recognition particle (SRP) subunit unique to chloroplasts, which has been shown to interact with the stroma-soluble C-terminus of the thylakoid-bound Albino3 insertase (Alb3-Cterm). In the chloroplast stroma, targeting to thylakoids is performed via the cpSRP pathway …


Hyper Stable Variants Of Fgf-1-Fgf-2 Dimer, Madison Shields Mcclanahan May 2022

Hyper Stable Variants Of Fgf-1-Fgf-2 Dimer, Madison Shields Mcclanahan

Chemistry & Biochemistry Undergraduate Honors Theses

Fibroblast Growth Factors (FGFs), including FGF-1 and FGF-2, are proteins that play a crucial role in cell proliferation, cell differentiation, cell migration, and tissue repair. FGF-1 and FGF-2 are useful in accelerating the healing process in the human body; however, these proteins are naturally thermally unstable, resulting in a relatively low half-life in vivo. 1,8 In efforts to improve the stability of this protein, FGF-1 and FGF-2 proteins are engineered by combining the amino acid sequences of the two proteins to form a heterodimer and obtain novel properties. These two FGF variants are chosen for their specific wound healing capabilities. …