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Biochemistry

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Iron-Sulfur Cluster Assembly; In Vivo Analysis Of The Methanogenic Suf System, Evan Dunkle Aug 2019

Iron-Sulfur Cluster Assembly; In Vivo Analysis Of The Methanogenic Suf System, Evan Dunkle

LSU Master's Theses

Iron-sulfur (Fe-S) clusters are among the most ancient and prevalent of all biological cofactors. Their assembly into associated proteins is a tightly regulated process with many organisms employing multiple cluster assembly pathways. Much is known about Fe-S cluster assembly in aerobic organisms such as Escherichia coli (E. coli) but little is known in regards to cluster assembly in more ancient organisms such as methanogens. Methanogens are members of the domain of Archaea and are defined by their ability to generate methane as a byproduct of their main energy generating pathway. Methanogens also have significantly higher Fe-S cluster content compared to ...


Knob-Socket Investigation Of Stability And Specificity In Alpha-Helical Secondary And Quaternary Packing Structure, Taylor Renee Rabara Jan 2019

Knob-Socket Investigation Of Stability And Specificity In Alpha-Helical Secondary And Quaternary Packing Structure, Taylor Renee Rabara

University of the Pacific Theses and Dissertations

The novel knob-socket (KS) model provides a construct to interpret and analyze the direct contributions of amino acid residues to the stability in α-helical protein structures. Based on residue preferences derived from a set of protein structures, the KS construct characterizes intra- and inter-helical packing into regular patterns of simple motifs. The KS model was used in the de novo design of an α-helical homodimer, KSα1.1. Using site-directed mutagenesis, KSα1.1 point mutants were designed to selectively increase and decrease stability by relating KS propensities with changes to α-helical structure. This study suggests that the sockets from the KS ...


Structural Characterization Of Black Widow Spider Dragline Silk Proteins Crp1 And Crp4, Mikayla Shanafelt Jan 2019

Structural Characterization Of Black Widow Spider Dragline Silk Proteins Crp1 And Crp4, Mikayla Shanafelt

University of the Pacific Theses and Dissertations

Spider dragline silk is a biomaterial with outstanding material properties, possessing high-tensile strength and toughness. In nature, dragline silk serves a central role during spider locomotion and web construction. Today, scientists are racing to elucidate the molecular machinery governing silk extrusion, attempting to translate this knowledge into a mimicry process in the laboratory to create synthetic fibers for a wide range of different applications. During extrusion, it has been established that biochemical and mechanical forces govern spidroin folding, aggregation, and assembly. In black widow spiders, at least 7 different proteins have been identified as constituents of dragline silk fibers. These ...


Evaluating Methods Of Obtaining Male Pheromone From Hymenochirus Sp. Using Analytical Chemistry, Vincent Wing-Kun Leung Jan 2019

Evaluating Methods Of Obtaining Male Pheromone From Hymenochirus Sp. Using Analytical Chemistry, Vincent Wing-Kun Leung

University of the Pacific Theses and Dissertations

Male Hymenochirus sp. frogs are known to release pheromone that attracts females of the same species. Four methods for collecting secretions containing pheromone in Hymenochirus sp. were tested: norepinephrine injection, gonadotropin-releasing hormone injection, homogenization of gland tissue, and electrostimulation of the skin over the breeding gland area. The samples collected were analyzed using high-performance liquid chromatography (HPLC) and mass spectrometry. The HPLC chromatograph for the male norepinephrine sample contained a peak at 6.4 min that was not in the female norepinephrine sample HPLC chromatograph. The male norepinephrine sample mass spectrum had a peak of m/z 292.0 not ...


Blubber Transcriptome And Proteome Responses To Repeated Adrenocorticotropic Hormone Administration In A Marine Mammal, Jared Deyarmin Jan 2019

Blubber Transcriptome And Proteome Responses To Repeated Adrenocorticotropic Hormone Administration In A Marine Mammal, Jared Deyarmin

University of the Pacific Theses and Dissertations

Chronic physiological stress impacts animal fitness by catabolizing metabolic stores and suppressing reproduction and immunity. This can be especially deleterious for capital breeding carnivores, such as marine mammals, which rely on lipid stores accrued during intensive foraging to sustain prolonged periods of fasting associated with reproduction. Therefore, chronic stress may cause a decrease in fitness in these animals, leading to population declines and potentially detrimental shifts in food web dynamics as a result. However, the impacts and indicators of chronic stress in animals are currently poorly understood. To identify downstream mediators of repeated stress responses in marine mammals, adrenocorticotropic hormone ...


Application And Comparison Of Active Learning Implementation Methods In Biochemistry Education, Dylan Thibaut Jan 2019

Application And Comparison Of Active Learning Implementation Methods In Biochemistry Education, Dylan Thibaut

Honors Undergraduate Theses

Biochemistry has continued to be one of the most complex and important subjects in science education. The purpose of this research is to investigate active learning implementation methods in a Biochemistry I context to determine the most effective means of preparing current science undergraduates. Two Biochemistry I classes over two semesters were analyzed in this study, with class A using a variable active learning schedule and class B using a consistent active learning schedule. Four aspects were analyzed to determine active learning validity: perception of different active learning properties, standardized final exam grades, class grade, and teaching implementation. The consistent ...


Genotyping For Response To Physical Training, Stacy Simmons Jan 2019

Genotyping For Response To Physical Training, Stacy Simmons

Browse all Theses and Dissertations

Understanding the inter-individual variability in physical fitness performance has been the focus of scientific research for decades especially in the United States military. Injury and physical inadequacy cost the U.S military millions of dollars every year. The project PHITE (Precision High Intensity Training through Epigenetics) was funded to investigate this personal complex trait by combing the genetic and epigenetic (non-shared environmental factors) contributions into a single model for physical training response. This project is set up as having 150 male and female recruits between the ages of 18-27 years old. Each participant is randomly put blind into either a ...


∆Np63Α Positively Regulates Erk3 Expression In Non-Melanoma Skin Cancer, Eid Salem Alshammari Jan 2019

∆Np63Α Positively Regulates Erk3 Expression In Non-Melanoma Skin Cancer, Eid Salem Alshammari

Browse all Theses and Dissertations

Non-melanoma skin cancer (NMSC) is a group of skin cancer that includes basal cell carcinoma of the skin (BCC), squamous cell carcinoma of the skin (SCC), actinic keratoses, a precursor to SCC, and other rare cutaneous carcinomas. p63, a member of the p53 gene family, is an important regulator for epithelial tissue growth and development. ∆Np63α, a main isoform of p63, is highly expressed in NMSC and plays essential roles in NMSCs development. Extracellular signal-regulated kinase 3 (ERK3) is an atypical member of the MAPK family. It possesses a single phosphorylation site (serine 189) in its activation loop, which makes ...


Serinc5: Its Sensitivity To Nef And Restriction Of Hiv-1, Weiwei Dai Aug 2018

Serinc5: Its Sensitivity To Nef And Restriction Of Hiv-1, Weiwei Dai

GSBS Dissertations and Theses

The accessory protein Nef of human immunodeficiency virus type 1 (HIV-1) has long been known to enhance the infectivity of HIV-1 progeny virions. The multipass transmembrane proteins serine incorporator 3 (SERINC3) and SERINC5 were recently identified as novel antiviral proteins that restrict HIV-1 infectivity. Nef enhances HIV-1 infectivity by removing SERINCs from the plasma membrane, which prevents their incorporation into progeny HIV-1 virions. To exploit this potent intrinsic antiretroviral factor for potential therapy development, it is critical to explore the determinants in SERINC5 that govern its downregulation by Nef and its restriction on HIV-1 infectivity. Here I report that the ...


Regulation Of The Pi3-Kinase/Pten Signaling Pathway By Tgf-Β In Prostate Cancer Cells, Mawiyah Kimbrough-Allah May 2018

Regulation Of The Pi3-Kinase/Pten Signaling Pathway By Tgf-Β In Prostate Cancer Cells, Mawiyah Kimbrough-Allah

Electronic Theses & Dissertations Collection for Atlanta University & Clark Atlanta University

Transforming growth factor -β (TGF-β) plays an important role in the progression of prostate cancer. It acts as a tumor suppressor in normal epithelial cells but as a tumor promoter in advanced prostate cancer cells. The PI3-kinase pathway has been shown to play integral roles in many cellular processes including cell proliferation, survival, and cell migration in many cell types. PI3-kinase pathway mediates TGF-β effects on prostate cancer cell migration and invasion. Phosphatase and tensin homolog (PTEN), a tumor suppressor gene, inhibits PI3-kinase pathway and is frequently mutated in prostate cancers. In this present study, we investigated possible roles of ...


The Role Of Dynamics Within Bama, The Central Component Of The Bam Complex, Pamela Arden Doerner Barbour Jan 2018

The Role Of Dynamics Within Bama, The Central Component Of The Bam Complex, Pamela Arden Doerner Barbour

Chemistry & Biochemistry Graduate Theses & Dissertations (1986-2018)

BamA is an essential component of the β-­‐barrel assembly machine that folds and inserts outer membrane proteins (OMPs) into the outer membrane of Gram-­‐negative bacteria. BamA is an OMP itself comprised of two domains, a soluble periplasmic N-­‐terminal domain consisting of five polypeptide transport associated (POTRA) repeats and a C-­‐terminal 16-­‐stranded β-­‐barrel domain. The mechanism of BamA is poorly understood but structural data suggests BamA is a dynamic protein with respect to the POTRA domains and barrel. The POTRA domains, numbered 1-5 from the N- to C- termini, can be divided into two sub-domains ...


Understanding The Structural Basis Of Sike Interactions, John Catalano Jan 2018

Understanding The Structural Basis Of Sike Interactions, John Catalano

Honors Theses

Tank Binding Kinase 1 (TBK1) acts as a catalytic hub in the regulation of numerous immune signaling pathways. Suppressor of IκB Kinase ε (SIKE) was recently characterized as a substrate of TBK1 whose binding properties are modulated by phosphorylation state, but very little is currently known about its function. However, because SIKE is known to form a dimer with itself, previous work generated a list of potential SIKE partners based on other proteins that contain sequences homologous to SIKE. Here, computational models of four potential SIKE partners, Heavy Chain myosin, tubulin, Beta Catenin and Ezrin, were generated and docked with ...


Production Of Synthetic Spider Silk, Ryan Matthew Hekman Jan 2018

Production Of Synthetic Spider Silk, Ryan Matthew Hekman

University of the Pacific Theses and Dissertations

Spider silk is a material that both has impressive mechanical properties and is also environmentally friendly. Though there are limitless potential engineering applications for such materials, industrial production of spider silk has proven to be challenging. Farming silk from spiders, as is done with silkworms, is not a viable option for large-scale production of spider silk due to the venomous and predatory nature of spiders. Here, an attempt is made to express synthetic spider silk minifibroins heterologously in Escherichia coli, to purify the recombinant spidroins from cell lysate, and to spin them into artificial fibers through a biomimetic process. Silk ...


Mass Action Modeling Of Catalysis Through Reaction Flux Estimation, Ethan Stancliffe Jan 2018

Mass Action Modeling Of Catalysis Through Reaction Flux Estimation, Ethan Stancliffe

Honors Theses at the University of Iowa

The complexity of biochemical networks necessitates the use of computational and mathematical frameworks to accurately characterize and study these systems. However, modern frameworks developed for this task have inadequacies that limit their accuracy or scalability. In this report, a mathematical model of the canonical enzyme substrate binding network is developed, and, using estimated true and maximal reaction rates, a methodology utilizing principles of flux balance analysis is developed to deduce the individual reaction rate constants in the network. It is then shown that these two reaction rates are not sufficient to unambiguously define a mass action kinetic model of this ...


Dissecting The Molecular Basis Of The Scaffold Protein Jade In Hbo1 Histone Acetyltransferase (Hat) Activity, Joseph Han Jan 2018

Dissecting The Molecular Basis Of The Scaffold Protein Jade In Hbo1 Histone Acetyltransferase (Hat) Activity, Joseph Han

Publicly Accessible Penn Dissertations

HBO1 is a member of the human MYST family of acetyltransferases that is evolutionarily conserved from yeast to human. HBO1 functions in the context of a multi-protein histone acetyltransferase (HAT) complex containing JADE1/2/3, HBO1, ING4/5 and Eaf6 to regulate DNA replication, transcription, and other important cellular processes. HBO1 is shown to be responsible for the majority of H4 acetylation throughout the human genome. HBO1 functions in many important biological processes such as interaction with the origin recognition complex (ORC) and loading of the minichromosome maintenance protein complex (MCM), highlighting its importance in DNA replication. In addition, HBO1 ...


Il-17 Drives Copper Uptake And Activation Of Growth Pathways In Colorectal Cancer Cells In A Steap4-Dependent Manner, Evan Martin Jan 2018

Il-17 Drives Copper Uptake And Activation Of Growth Pathways In Colorectal Cancer Cells In A Steap4-Dependent Manner, Evan Martin

ETD Archive

Colorectal cancer is a disease characterized by abnormal, invasive cell growth beginning in the colon or rectum. The third most common type of cancer worldwide, approximately one million new cases of the disease are diagnosed across the globe annually, resulting in an estimated 700,000+ deaths. One major risk factor associated with development of colorectal cancer is the presence of chronic inflammation in the large intestine, also known as colitis. Inflammation is a complex immune response against harmful stimuli, characterized by symptoms including heat, redness, swelling and pain. One important molecular mediator of this process is interleukin 17 (IL-17), a ...


Il-17 Drives Copper Uptake And Activation Of Growth Pathways In Colorectal Cancer Cells In A Steap4-Dependent Manner, Evan Martin Jan 2018

Il-17 Drives Copper Uptake And Activation Of Growth Pathways In Colorectal Cancer Cells In A Steap4-Dependent Manner, Evan Martin

ETD Archive

Colorectal cancer is a disease characterized by abnormal, invasive cell growth beginning in the colon or rectum. The third most common type of cancer worldwide, approximately one million new cases of the disease are diagnosed across the globe annually, resulting in an estimated 700,000+ deaths. One major risk factor associated with development of colorectal cancer is the presence of chronic inflammation in the large intestine, also known as colitis. Inflammation is a complex immune response against harmful stimuli, characterized by symptoms including heat, redness, swelling and pain. One important molecular mediator of this process is interleukin 17 (IL-17), a ...


Avicin Is A Potent Sphingomyelinase Inhibitor That Blocks K-Ras Plasma Membrane Interaction And Its Oncogenic Activity, Christian M. Garrido Jan 2018

Avicin Is A Potent Sphingomyelinase Inhibitor That Blocks K-Ras Plasma Membrane Interaction And Its Oncogenic Activity, Christian M. Garrido

Browse all Theses and Dissertations

Ras proteins are small GTPases that regulate cell growth, differentiation and apoptosis. There are three main isoforms: H-, N-, and K-Ras in mammalian cells, and they cycle between an active GTP- and inactive GDP-bound states. Constitutively active Ras mutations are found in ~15% of all human cancers. Of those, oncogenic K-Ras is found in ~98% of pancreatic, ~52% colorectal, and ~32% of lung cancers. In nearly 30 years since its discovery, there are no anti-K-Ras drugs currently available for clinical use. Since K-Ras must be localized to the plasma membrane (PM) for its full biological activity, targeting K-Ras PM interaction ...


Discovery Of Small Molecules Blocking Oncogenic K-Ras Activity, Sarah E. Kovar Jan 2018

Discovery Of Small Molecules Blocking Oncogenic K-Ras Activity, Sarah E. Kovar

Browse all Theses and Dissertations

Ras proteins were the first human oncogenes discovered. Although Ras has been found to be the most frequently mutated oncogene, there are currently no anti-Ras-specific drugs available in the clinic. Ras is responsible for initiating cellular pathways that include proliferation, survival, and apoptosis. There are three ubiquitously expressed Ras isoforms in mammalian cells: H-, N-, and K-Ras. Interaction with the plasma membrane is required for Ras biological activity. When Ras interaction with the plasma membrane is blocked, Ras activity is inhibited. Two compounds (from Dr. Ketcha, WSU Chemistry Department) were tested and shown to dissociate K-Ras, but not H-Ras from ...


Identification Of Factors Involved In 18s Nonfunctional Ribosomal Rna Decay And A Method For Detecting 8-Oxoguanosine By Rna-Seq, Kelly A. Limoncelli Dec 2017

Identification Of Factors Involved In 18s Nonfunctional Ribosomal Rna Decay And A Method For Detecting 8-Oxoguanosine By Rna-Seq, Kelly A. Limoncelli

GSBS Dissertations and Theses

The translation of mRNA into functional proteins is essential for all life. In eukaryotes, aberrant RNAs containing sequence features that stall or severely slow down ribosomes are subject to translation-dependent quality control. Targets include mRNAs encoding a strong secondary structure (No-Go Decay; NGD) or stretches of positively-charged amino acids (Peptide-dependent Translation Arrest/Ribosome Quality Control; PDTA/RQC), mRNAs lacking an in-frame stop codon (Non-Stop Decay; NSD), or defective 18S rRNAs (18S Nonfunctional rRNA Decay; 18S NRD). Previous work from our lab showed that the S. cerevisiae NGD factors DOM34 and HBS1, and PDTA/RQC factor ASC1, all participate in the ...


The Crowding Effects Of Rmlc On R67 And Chromosomal Dihydrofolate Reductase Enzymes, Michael A. Craig May 2017

The Crowding Effects Of Rmlc On R67 And Chromosomal Dihydrofolate Reductase Enzymes, Michael A. Craig

Chancellor’s Honors Program Projects

No abstract provided.


The Impact Of Socs1 And Socs3 Peptide Mimetics On Rho And Cdc42 Proteins Expression, F-Actin Cytoskeleton Rearrangements, And Cytokines Production Of Uninfected And Hsv-1 Infected M1 And M2 Raw 264.7 Murine Macrophages, Maha A. Elwardany Jan 2017

The Impact Of Socs1 And Socs3 Peptide Mimetics On Rho And Cdc42 Proteins Expression, F-Actin Cytoskeleton Rearrangements, And Cytokines Production Of Uninfected And Hsv-1 Infected M1 And M2 Raw 264.7 Murine Macrophages, Maha A. Elwardany

Browse all Theses and Dissertations

The immune system plays an essential role in the pathogenesis of HSV-1 during the lytic phase of the disease, orchestrating the inflammatory response, retaining the virus in its latent phase and preventing the recurrence of HSV-1 infection. Macrophages display a vital role in the innate and adaptive immune responses during multiple phases of HSV-1 infection. Polarized macrophages are categorized into two distinct classes with diverse functions. The classically activated M1 can engulf and destroy the microbial agents, produce proinflammatory cytokines, and participate in the pathogenesis of many inflammatory diseases. The alternatively activated M2 induces anti-inflammatory mediators and stimulates tissue remodeling ...


Functional And Structural Analyses Of A Bacterial Antifreeze Protein, Chen Wang Jan 2017

Functional And Structural Analyses Of A Bacterial Antifreeze Protein, Chen Wang

LSU Doctoral Dissertations

Antifreeze proteins (AFPs) are a class of ice binding proteins (IBPs) that are expressed by different cold-adapted organisms to increase their freezing tolerance. AFPs have two major properties: thermal hysteresis and ice recrystallization inhibition. Here we report the functional and structural analyses of a bacterial AFP, IBPv. IBPv was originally secreted by a bacterium recovered from a deep glacial ice core drilled at Vostok Station, Antarctica. Our study showed that the recombinant protein rIBPv exhibited a thermal hysteresis of 2°C at concentrations higher than 50 µM, effectively inhibited ice recrystallization, and enhanced bacterial viability during freeze-thaw cycling. Circular dichroism ...


The Function Of Renalase, Brett Allen Beaupre Aug 2016

The Function Of Renalase, Brett Allen Beaupre

Theses and Dissertations

Renalase was originally reported to be an enzyme secreted into the blood by the kidney to lower blood pressure and slow heart rate. Despite multiple reports claiming to confirm this activity in vivo there has been considerable discord in regards to the reaction catalyzed by renalase. The structural topology of renalase resembles that of known flavoprotein oxidases, monooxygenases and demethylases, but the conserved active site residues are unique to renalase. It has been reported that the catalytic function of renalase is to oxidize circulating catecholamines, however in vitro studies have failed to demonstrate a catalytic activity in the presence of ...


Functional Characterization Of Dasciz In Gene Expression And Development In Drosophila Melanogaster, Saheli Sengupta Jan 2016

Functional Characterization Of Dasciz In Gene Expression And Development In Drosophila Melanogaster, Saheli Sengupta

Graduate Theses and Dissertations

A protein may perform various functions inside a cell through multiple signaling networks and help in fine-tuning cellular activities required to maintain complex physiology. A large number of proteins have been described that act as both stress response proteins as well as transcription factors in gene expression related to development. These functions may or may not be interlinked depending on the protein under consideration. For example, Sp1 was initially described to act as a transcription factor regulating the expression of a large number of essential genes. Later, it was also implicated in DNA damage response and in recent studies, has ...


Electron Transfer And Redox Chemistry In Hexa-Coordinate Hemoglobins, Navjot Singh Jan 2016

Electron Transfer And Redox Chemistry In Hexa-Coordinate Hemoglobins, Navjot Singh

Graduate Theses and Dissertations

The heme prosthetic group can be held into proteins in a variety of ways. Most often amino acid side chains coordinate one or both of the two available axial coordination sites of the heme iron. Coordination of both sites, such as in cytochrome b5, produces a good electron transfer protein but excludes the binding of exogenous ligands. In hemoglobins, coordination can occur at a single site (as in the “pentacoordinate” hemoglobins associated with oxygen transport), or at both sites (as in the “hexacoordinate” hemoglobins found in a wider distribution of organisms and functions). Surprisingly, hexacoordination in hemoglobins is usually reversible ...


Amylolysis Of Eight Different Starches With Four Different Species Of Alpha-Amylase, Robert Leonard Sheets Jan 2016

Amylolysis Of Eight Different Starches With Four Different Species Of Alpha-Amylase, Robert Leonard Sheets

Graduate Theses and Dissertations

Presented here are the action of four different Α-amylases on eight different starches in their native granular form. Of the starches, potato and amylomaize-7 were slowest to degrade, but maize, wheat, rice, barley, and tapioca degraded at a similar (and faster) rates. Waxy maize degraded most rapidly compared to the other starches. Amylases from Bacillus licheniformis and human saliva were significantly more effective than amylases from Bacillus amyloliquefaciens and porcine pancreas. The broad range of outcomes indicates the correct choice of enzyme and starch is a critical factor in the design of efficient protocols for starch processing in the bio-renewable ...


Exploring Genetic-Based Metabolic And Morphological Diversity Of Arabidopsis Thaliana Ecotypes Influenced By The Environment, Jennifer R. Robinson Jan 2016

Exploring Genetic-Based Metabolic And Morphological Diversity Of Arabidopsis Thaliana Ecotypes Influenced By The Environment, Jennifer R. Robinson

Graduate Theses and Dissertations

As concerns regarding climate change continue to rise, it is essential to understand how the environment affects the natural variation of existing biological diverse plants. Eight different Arabidopsis thaliana ecotypes (Col-0, Bay-0, Bur-0, Tsu-1, Sha, Est-1, Cvi-0, and Ler-1) were grown under two different growth conditions, 18 °C and 24 °C, in order to understand how the effect of environmental stress (temperature) and genetic background impacts the organism’s natural phenotypic variation. Morphometric analysis of morphological traits (root length, rosette area, inflorescence length, seed size and silique size) and metabolic profiling of aerial leaf tissue (extracellular lipids), closed flower buds ...


Contributions Of Sequence And Structure To Ligand Selectivity In Class Ii Cobalamin Riboswitches, Samantha M. Webster Jan 2016

Contributions Of Sequence And Structure To Ligand Selectivity In Class Ii Cobalamin Riboswitches, Samantha M. Webster

Undergraduate Honors Theses

Riboswitches are gene regulatory elements found in the 5’-untranslated region of many bacterial genes. The direct binding of small molecule ligands induces conformational changes in the RNA that influence downstream expression machinery and determine the transcription or translation of an attached gene. Cobalamin riboswitches, which bind coenzyme-B12 and other cobalamin variants, are divided into two distinct classes. Cbl-I riboswitches contain a large peripheral element that limits riboswitch binding to only coenzyme-B12 (adenosylcobalamin, or AdoCbl). Cbl-II riboswitches do not contain the same peripheral element, and were originally thought to only bind smaller species of cobalamin (including methylcobalamin, or ...


Structure And Function Of The Plasmodium Falciparum Apicoplast Dna Polymerase: The First Look At An "Atypical" A-Family Polymerase And Its Potential In Antimalarial Drug Discovery, Morgan Eilise Milton Jan 2016

Structure And Function Of The Plasmodium Falciparum Apicoplast Dna Polymerase: The First Look At An "Atypical" A-Family Polymerase And Its Potential In Antimalarial Drug Discovery, Morgan Eilise Milton

Graduate Theses and Dissertations

The leading cause of malaria infections in humans is the parasite Plasmodium falciparum. The parasite contains a non-photosynthetic plastid-like organelle called the apicoplast, which is essential for its survival within the host. The apicoplast maintains its own genome, which must undergo replication and repair. The only DNA polymerase in the apicoplast (apPOL) is classified as an atypical A-family polymerase. apPOL shares no direct orthology to mammalian polymerases, making the P. falciparum apicoplast DNA polymerase an attractive anti-malarial drug target. We solved the crystal structure of P. falciparum apPOL, the first structural representative of the atypical A-family polymerases. We showed that ...