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Full-Text Articles in Biochemistry

Interfacial Interactions Between Engineered Nanoplastics And Biological Systems: Towards An Atomic And Molecular Understanding Of Plastics- Driven Cellular Dyshomeostasis, Afroz Karim Dec 2023

Interfacial Interactions Between Engineered Nanoplastics And Biological Systems: Towards An Atomic And Molecular Understanding Of Plastics- Driven Cellular Dyshomeostasis, Afroz Karim

Open Access Theses & Dissertations

The persistent presence of micro (nano) plastics in our environment has raised concerns regarding potential health risks associated with human exposure. With the extensive use of plastic materials and the widespread consumption of plastic-contaminated food items, two types of microplastics, polystyrene (PS) and polymethylmethacrylate (PMMA), have attracted increased attention. While the adverse effects of microplastics on animals and marine life have been extensively studied, their potential impact on human health remains largely unexplored. Specifically, the interaction between microplastics and biomolecules within the human body and their effect on human health have yet to be comprehensively investigated. This dissertation study focuses …


X-Ray Crystal Structure Of E399q,E708q Ecm16 Double Mutant, Gileydis Guillama Aug 2023

X-Ray Crystal Structure Of E399q,E708q Ecm16 Double Mutant, Gileydis Guillama

Open Access Theses & Dissertations

The use of antibiotics has undoubtedly been a boon for humanity in combating infections and microbial threats. However, their widespread utilization has contributed to the emergence and spread of antibiotic resistance, which now poses a significant public health challenge. Streptomyces bacterium, produce diverse secondary metabolites with antibacterial, antifungal, antiviral, antitumoral, and immunosuppressant activities. Among these compounds is echinomycin, a nonribosomal peptide antibiotic synthesized by Streptomyces lasalocidi, which inhibits DNA replication and transcription by intercalating the DNA duplex at CpG steps. A gene called ecm16 was identified in the echinomycin biosynthetic gene cluster, which provides echinomycin self-resistance. Ecm16 recognizes DNA duplexes …


Structural Study Of Lsd13 And Lsd14 Type I Modular Polyketide Synthases From The Lasalocid A Biosynthesis Pathway, Dayan Viera Aug 2023

Structural Study Of Lsd13 And Lsd14 Type I Modular Polyketide Synthases From The Lasalocid A Biosynthesis Pathway, Dayan Viera

Open Access Theses & Dissertations

Bioactive natural products often possess a complex structure and have a large size which make their chemical synthesis highly challenging. To overcome this challenge, we are developing a biosynthetic method for production of natural products and their analogs. This technology is expected to decrease the synthesis time from years to weeks and reduce the cost of drug production by multiple orders of magnitude. We are investigating the biosynthesis pathway of lasalocid A, an anticancer antibiotic, to develop this technology. Specifically, we aim to characterize the enzymes structurally and biochemically in this pathway, thus paving the way for their rational engineering. …


Development Of A Ph-Triggered Cargo Delivery System With Esxa Mutants, Shuchen Chen Aug 2022

Development Of A Ph-Triggered Cargo Delivery System With Esxa Mutants, Shuchen Chen

Open Access Theses & Dissertations

Tuberculosis (TB) is a communicable disease caused by Mycobacterium tuberculosis (Mtb). It was the leading cause of human death generated by a single infectious agent before the Coronavirus (COVID-19) pandemic. Mtb has a special mechanism to evade the hostâ??s immune system and utilize macrophages as reservoirs. Latent TB infections have been a threat to public health. Liposome has been widely used for drug delivery. Immunoliposomes are special liposome carriers coated with ligands, such as antigens, targeting certain cells or organs to regulate the uptake of liposome. By constructing the liposome components, or surface modification, cargo release of liposome can be …


Eluication Of Lipid Metabolic Pathways In Differentiating Giardia Lamblia Using High Resolution Mass Spectrometry, Cameron Ellis Aug 2022

Eluication Of Lipid Metabolic Pathways In Differentiating Giardia Lamblia Using High Resolution Mass Spectrometry, Cameron Ellis

Open Access Theses & Dissertations

Giardia lamblia is an intestinal protozoan found worldwide, including the U.S. This parasite exists in two morphologic stages - a replicative trophozoite and a relatively dormant yet viable cyst. While exposures of cysts to gastric acid during passage through the human stomach induces excystation, factors in the small intestine, where trophozoites colonize trigger encystation or cyst formation. Transformation into cyst stage is essential for Giardia to survive in the environment for months before infecting new hosts. Because of its small genome size (11.7 Mb), metabolic pathways in Giardia are highly reduced. As far as lipid metabolism is concerned, only limited …


Characterization Of Esxa/Esxb Heterodimer Membrane Interaction With A Novel Popc/Popg Liposome Model, Salvador Vazquez Vazquez Reyes Aug 2022

Characterization Of Esxa/Esxb Heterodimer Membrane Interaction With A Novel Popc/Popg Liposome Model, Salvador Vazquez Vazquez Reyes

Open Access Theses & Dissertations

EsxA and EsxB are co-secreted as a heterodimer and have been shown to play critical roles in phagosome rupture and translocation of Mycobacterium tuberculosis into the cytosol. Current in vitro studies support a model in which the EsxA:EsxB heterodimer is dissociated upon acidification, which might allow EsxA insertion into liposome membranes. While the membrane permeabilizing activity (MPA) of EsxA has been well characterized in liposomes composed of di-oleoyl-phosphatidylcholine (DOPC), the MPA of EsxA:EsxB heterodimer has not been detected with the DOPC liposome. In this study, we established a new in vitro membrane assay to test the MPA of EsxA and …


Nanotechnology-Based Approaches To Mitigate Environmental Pollutants -- Induced Neurological Disorders, Jyoti Ahlawat May 2022

Nanotechnology-Based Approaches To Mitigate Environmental Pollutants -- Induced Neurological Disorders, Jyoti Ahlawat

Open Access Theses & Dissertations

Neurodegenerative diseases such as Parkinson's disease (PD), Alzheimerâ??s Disease (AD) and Huntingtonâ??s Disease (HD) have no cure despite intensive research efforts geared towards therapeutics development. In the USA, patients with PD and AD alone cost the nation ~ $200 billion annually in patient care and lost productivity. Therefore, there remains an urgent and unmet need to develop novel drugs and drug carriers with the potential to slow down, halt and ideally reverse the course of neurodegenerative disorders. The dissertation focuses on developing approaches towards targeting PD using multifactorial mechanisms including the targeting of protein aggregation and oxidative stress. This is …


Small Heat Shock Protein 27 And Its Role In Human Disease, Bianka Andrea Holguin May 2022

Small Heat Shock Protein 27 And Its Role In Human Disease, Bianka Andrea Holguin

Open Access Theses & Dissertations

Small heat shock protein 27 (Hsp27) is a ubiquitously expressed molecular chaperone with roles in many physiological processes. As an ATP-independent molecular chaperone, Hsp27 protects substrates from irreversible aggregation and holds them in a folding competent state for later recycling into the proteome. Hsp27 proteins form dimers that are assembled into large oligomeric complexes. Phosphorylation of Hsp27 dissembles the oligomers into chaperone active dimers. Several missense mutations of Hsp27 are causative for the neurodegenerative disorders Charcot-Marie-Tooth disease 2F and distal Hereditary Motor Neuropathy IIB. Here I show that the oligomerization and chaperoning ability of Hsp27 are altered by the Hsp27 …


Structural And Biochemical Studies On Disease Associated Proteins: Heat Shock Protein 60 And Hiv Capsid, Alejandro Rodriguez Apr 2022

Structural And Biochemical Studies On Disease Associated Proteins: Heat Shock Protein 60 And Hiv Capsid, Alejandro Rodriguez

Open Access Theses & Dissertations

Structural studies on proteins provide valuable knowledge, from information about their fundamental nature, to laying a foundation for rational drug design. Here, we study two proteins, a human mitochondrial chaperonin heat shock protein 60 (Hsp60) and the main structural HIV-1 protein capsid (CA). We focus on the structural nature of both proteins to try to understand their role in disease and elucidate the mechanism of potential drug treatments. Hsp60 is a chaperonin found in human mitochondria that is responsible for assisting client proteins reach their native, functional, state. The mechanism by which it catalyzes protein folding, however, has not been …


Molecular Mechanism Of Dna Bisintercalator Antibiotic Resistance, Priyanka Rajendra Gade Dec 2021

Molecular Mechanism Of Dna Bisintercalator Antibiotic Resistance, Priyanka Rajendra Gade

Open Access Theses & Dissertations

Class II UvrA is an ATP-binding cassette protein and a homolog of class I UvrA, the DNA lesion detection component of the universal prokaryotic nucleotide excision repair system. We show that Ecm16, a class II UvrA protein from Streptomyces lasalocidi, specifically recognizes DNA duplex that contains the DNA bisintercalator antibiotic echinomycin. Heterologous expression of Ecm16 in Escherichia coli renders host cells resistant to echinomycin. Interestingly, Ecm16’s antibiotic resistance activity does not require the DNA repair proteins UvrA/B/C/D, indicating that it operates independently of the cell’s nucleotide excision repair pathway. Unlike UvrA, Ecm16 uses the insertion domain to regulate its ATPase …


Structural Characterization Of Two Large Icosahedral Dna Viruses And Their Capsid Assembly Mechanisms, Yuejiao Xian Dec 2020

Structural Characterization Of Two Large Icosahedral Dna Viruses And Their Capsid Assembly Mechanisms, Yuejiao Xian

Open Access Theses & Dissertations

In the last three decades, many large DNA viruses were discovered and grouped into a loosely defined clade of Nucleocytoplasmic Large DNA Viruses (NCLDVs). NCLDVs infect a wide range of hosts from single cellular protists to large animals. Recently, these viruses were classified as a new phylum of Nucleocytoviricota under the kingdom of Bamfordvirae. The genomes of these Nucleocytoviricota viruses (NCVs) are remarkedly large and complicated, containing many cellular genes from all three domains of life, which raised intensive debates on their evolutionary origins. Despite being classified in the same phylum, their physical structures vary and can be roughly classified …


Insights Into The Structure, Pharmacology, And Evolution Of The Glycine Transporter 2, Ashley Bryan Lopez Jan 2020

Insights Into The Structure, Pharmacology, And Evolution Of The Glycine Transporter 2, Ashley Bryan Lopez

Open Access Theses & Dissertations

The balance between neuronal excitation and inhibition in the central nervous system is vital for survival. Overexcitation can be toxic and lead to certain manias or even death. On the other hand, extremely low levels of inhibition cause hyperekplexia, pain, and even forms of autism. Neuronal inhibition is, for the most part, achieved by two neurotransmitters, GABA and glycine. Levels of both neurotransmitters in the synaptic cleft are meticulously regulated by the GABA and glycine transporters, respectively, which belong to the solute carrier 6 (SLC6) family of neurotransmitter transporters and share structural similarities with other family members. In Chapter 1, …


Structural Basis For The Stereoselective Epoxidation Reaction In Polyether Natural Product Biosynthesis, Qian Wang Jan 2020

Structural Basis For The Stereoselective Epoxidation Reaction In Polyether Natural Product Biosynthesis, Qian Wang

Open Access Theses & Dissertations

Polycyclic polyether natural products have received much attention due to their diverse biological activities, ranging from extreme toxicity to therapeutic properties, including antimicrobial, antifungal, and anticancer activities. They are featured by multiple cyclic ether groups that vary in the number, size, and arrangement. Ionophore polyethers contain multiple tetrahydrofuran and tetrahydropyran rings connected by either spiroketal systems or carbon-carbon single bonds. Over the past 40 years, significant progress has been made in deciphering polyether biosynThesis pathways. Remarkably, all members of the polycyclic polyether family are thought to be generated via a common biosynthetic scheme. In 1983, Cane, Celmer, and Westly proposed …


Molecular And Functional Characterization Of Α-Galactosyl Epitopes In Trypanosoma Cruzi, Uriel Ortega Rodriguez Jan 2020

Molecular And Functional Characterization Of Α-Galactosyl Epitopes In Trypanosoma Cruzi, Uriel Ortega Rodriguez

Open Access Theses & Dissertations

Trypanosoma cruzi, the causative agent of Chagas disease (CD) currently affects 6-7 million people across the world. Currently, only two drugs, benznidazole and nifurtimox, are available for treatment of CD and they are highly toxic and less effective in the chronic stage of the disease. Specific biomarkers for diagnosis and follow-up of treatment do not exist in the clinical settings. following chemotherapy, patients take approximately 10-20 years to exhibit negative seroconversion with the conventional serology assays. Moreover, there is no vaccine available to prevent or treat CD. T. cruzi contains a complex cell surface consisting of several classes of glycoconjugates …


Expression, Purification, And Characterization Of Recombinant Human Npas2, Brenda Moreno Jan 2020

Expression, Purification, And Characterization Of Recombinant Human Npas2, Brenda Moreno

Open Access Theses & Dissertations

Many living organisms have biological clocks known as circadian rhythms that control various physiological and behavioral processes, tailored with the day and night. At the cellular level, the circadian clock drives daily rhythms with a transcriptional-translational feedback loop (TTFL) established by multiple transcription factors and genes under their regulation. Circadian Locomotor Output Cycles Kaput (CLOCK) and Brain and Muscle ARNT-like protein 1 (BMAL1) are two of those transcription factors, initiating the TTFL by forming a heterodimeric complex that bind to DNA promoters. Neuronal PAS domain protein 2 (NPAS2) is a functional analog to CLOCK. Less knowledge about NPAS2, in contrast …


Antioxidant Intervention In Radical-Induced Protein Damage, Emmanuel Zubia Jan 2020

Antioxidant Intervention In Radical-Induced Protein Damage, Emmanuel Zubia

Open Access Theses & Dissertations

Many environmental toxicants are known to increase free-radical production, which can create cellular havoc and lead to a myriad of ailments. Antioxidants can be used to ameliorate the prevalence of free radicals, potentially serving as prophylactics against radical-induced disorders. Many exogenous antioxidants are phytochemicals in origin, such as ascorbic acid, gallic acid, and ellagic acid. Some of these antioxidants can be found in traditional medicine, like tanshinone and brazilin, which have been studied and are known to have low cytotoxicity. Here we test the radical rescue capacity of a selected group of phytochemical antioxidants on protein rescue models. Specifically, our …


Novel Methods For The Inactivation Of Cruzain For The Prevention And Treatment Of Chagas Disease, Veronica Gonzalez Jan 2019

Novel Methods For The Inactivation Of Cruzain For The Prevention And Treatment Of Chagas Disease, Veronica Gonzalez

Open Access Theses & Dissertations

Chagas Disease, also known as American Trypanosomiasis, is endemic to Latin American and is gradually making its way to other countries. The disease is caused by Trypanosoma cruzi, a protozoan parasite that causes lesions and inflammation of organs including the heart, esophagus, and colon. Over 30% of people infected will develop heart disease which can be fatal if untreated. While no vaccine is yet available, research is currently being conducted in finding new treatments for the disease. One target is an enzyme that is believed to help the progression of the disease. Cruzain, a cysteine protease expressed as a pro-enzyme, …


Potential Of Nanoscale Elements To Control Fusarium Wilt Disease In Tomato (Solanum Lycopersicum), Enhance Macronutrient Use Efficiency, And Increase Its Yield, Ishaq Olarewaju Adisa Jan 2019

Potential Of Nanoscale Elements To Control Fusarium Wilt Disease In Tomato (Solanum Lycopersicum), Enhance Macronutrient Use Efficiency, And Increase Its Yield, Ishaq Olarewaju Adisa

Open Access Theses & Dissertations

Nanotechnology has a great potential in ensuring food production, security and safety globally. Over the past decade, research on the use of nanomaterials to supply nutrient elements and protect plants from pest and diseases has significantly increased. Tomato (Solanum lycopersicum) is one of the most consumed vegetables in the world and United State is one of its largest producers globally generating billions of dollars annually in revenue.. Tomato plants are affected worldwide by Fusarium wilt caused by Fusarium oxysporum f. sp. Lycopersici. There is growing concern about excessive use of conventional pesticides in controlling Fusarium and other diseases in tomato …


Naturally Derived Compounds As Preventatives Of Proteinopathies, Lois Mendez Jan 2019

Naturally Derived Compounds As Preventatives Of Proteinopathies, Lois Mendez

Open Access Theses & Dissertations

Neurodegenerative diseases, such as Parkinson’s disease (PD), afflict millions worldwide. Of greater concern is the fact that a main risk factor this disease is aging and the baby boomer population is now reaching a geriatric age. Despite the active research in this area, little progress has been made in the development of therapeutic strategies and furthering of our understanding in pinpointing the causal events that onset these disease processes. Our lab has focused on studying the protein homeostasis of key biomarkers in neurodegenerative diseases and examining whether natural compounds can act as neuro-protectants and, thus, attenuate the pathology that ensues …


Steroid-Coa Ligases, Fadd17a1 And Fadd19a1, And Their Role In Cholesterol Side-Chain Degradation In Mycobacterium Tuberculosis, Johnathan Salim Abou-Fadel Jan 2018

Steroid-Coa Ligases, Fadd17a1 And Fadd19a1, And Their Role In Cholesterol Side-Chain Degradation In Mycobacterium Tuberculosis, Johnathan Salim Abou-Fadel

Open Access Theses & Dissertations

Mycobacterium tuberculosis (Mtb) is a serious health issue arising from the increasing incidence of multi-drug resistant (MDR-TB) strains that are becoming more prevalent in high-risk countries, especially here in the Texas/Mexico border. Confirmed cases and outbreaks in schools and hospitals are more frequent in this region due to the high-volume pedestrian traffic between the two cities, and the lack of a modernized health system in Mexico. Identification of new Mtb metabolic pathways for development of novel antitubercular drugs is urgently needed. The goal of this current work investigates two Mtb fatty acyl-CoA ligase enzymes' (FadD17A1 and FadD19A1) to explore whether …


The Structural And Functional Study Of The Human Mitochondrial Hsp60 Chaperonin In Neurodegenerative Diseases, Jinliang Wang Jan 2018

The Structural And Functional Study Of The Human Mitochondrial Hsp60 Chaperonin In Neurodegenerative Diseases, Jinliang Wang

Open Access Theses & Dissertations

Proteins are essential elements that are responsible for a variety of cellular activities within organisms, including catalyzing metabolic reactions, DNA replication, responding to stimuli, providing structure to cells and organisms, and transporting molecules. After protein synthesis in the ribosome, the unfolded protein need to fold into their unique compact structures so that they can perform their full biological functions. The biologically active structure of a protein is referred to the native-state of the protein with biological activity. The process of protein folding is one of the most important and challenging research topics of contemporary biochemistry, especially for its central role …


Integrated Immunoassays On Paper/Polymer Hybrid Microfluidic Devices For Low-Cost Detection Of Disease Biomarkers, Sanjay Sharma Timilsina Jan 2018

Integrated Immunoassays On Paper/Polymer Hybrid Microfluidic Devices For Low-Cost Detection Of Disease Biomarkers, Sanjay Sharma Timilsina

Open Access Theses & Dissertations

Infectious diseases and cancers have been the major cause of global death and disability causing a significant impact on global health and economies. Enzyme-linked immunosorbent assay (ELISA) is one of the most widely used laboratory diagnostic methods for infectious diseases and cancer. ELISA detects proteins based on their binding to immobilized antibodies or antigen. Even though most ELISAs performed today in 96-well plates are well suited for high throughput assays, performing ELISA in low-resource settings is limited by several factors, such as long incubation time, large volumes of precious reagents, and well-equipped laboratories. Herein, we have developed multiple simple, miniaturized …


Biochemical Characterization Of Wild-Type Hsp27 And Point Mutation S135f That Leads To Neurodegenerative Disease, Janelly Villalobos Jan 2017

Biochemical Characterization Of Wild-Type Hsp27 And Point Mutation S135f That Leads To Neurodegenerative Disease, Janelly Villalobos

Open Access Theses & Dissertations

HSPB1, also classified as heat shock protein 27 (Hsp27), is a small chaperone that is active in cells during stressful conditions. The chaperone can stabilize target proteins in a non-aggregated folding state and might be involved in regulation of folding and assembly of neurofilaments. There are five mutations in the genome of Hsp27 that are involved in Charcot Marie Tooth Disease (CMT). This neurodegenerative disease is characterized by the first decades of life where it slowly progresses to weakness of muscles followed by sensory loss and skeletal deformities. CMT is the most common hereditary neuromuscular disease, with an estimated rate …


The Human Mitochondrial Chaperonin: It Takes Two Single-Rings To Tango, Adrian Sergio Enriquez Jan 2017

The Human Mitochondrial Chaperonin: It Takes Two Single-Rings To Tango, Adrian Sergio Enriquez

Open Access Theses & Dissertations

The human mitochondrial chaperonin is a macromolecular machine that catalyzes the proper folding and assembly of newly imported mitochondrial proteins into their biologically active state. It is composed of two proteins from the highly conserved heat shock protein family, hsp10 and hsp60, that assemble into large oligomeric complexes responsible for mediating the folding of non-native polypeptides in an ATP dependent manner. In addition to its innate role in protein folding, human mitochondrial hsp60 has been implicated in numerous moonlighting cellular activities that have been linked to diseases conditions such as cancer and neurodegeneracy. In light of its cellular importance, the …


Structure And Biological Activity Of A D3g Mutation In The Human Mitochondrial Chaperonin Hsp60, Jihui Li Jan 2016

Structure And Biological Activity Of A D3g Mutation In The Human Mitochondrial Chaperonin Hsp60, Jihui Li

Open Access Theses & Dissertations

Proteins are essential components in all cellular activities, including signal transduction, gene expression regulation, immune response, structural support and many others. Following their synThesis on the ribosome, proteins need to fold into their precise three-dimensional structure to obtain functionality. If they fold incorrectly they are prone to aggregation and cause a wide range of neurodegenerative diseases. Some proteins are capable of folding without assistance but others need help from protein complexes known as chaperonins. Chaperonins are a family of proteins that assemble into barrel-shaped cages the create a protected chamber for misfolded proteins to refold into their biologically active state. …


Label-Free Quantitative Proteomics Reveals A Novel Sgta/Peroxiredoxin I Complex That Regulates Androgen Receptor Activity, Yenni Alejandra Garcia Jan 2016

Label-Free Quantitative Proteomics Reveals A Novel Sgta/Peroxiredoxin I Complex That Regulates Androgen Receptor Activity, Yenni Alejandra Garcia

Open Access Theses & Dissertations

The dynamic Hsp70-90 chaperone machinery along with its cochaperone partners are well-characterized for their ability to fold, assemble, and regulate steroid hormone receptors (SHRs). Human small glutamine rich tetratricopeptide repeat (TPR) containing protein alpha (SGTA) is a recently identified protein that has a characteristic Hsp90-binding TPR domain and is a key participant in the androgen, glucocorticoid, and progesterone receptor signaling pathway. In addition, SGTA plays a role in cellular processes such as cell cycle progression and apoptosis. We have demonstrated that SGTA binds directly to both Hsp70 (kd = 6 μM) and Hsp90 (kd = 11 μM). In a cell-free …


Identifying Non-Classical Active Sites As A Tool For Enzyme Inhibition, Marisol Serrano Jan 2016

Identifying Non-Classical Active Sites As A Tool For Enzyme Inhibition, Marisol Serrano

Open Access Theses & Dissertations

Chagas disease, caused by the parasite Trypanosoma cruzi, is an endemic life-threatening disease that affects mainly the heart. It remains the leading cause of heart failure in Latin American countries. Since current treatments against this parasite are highly toxic and somewhat ineffective, novel and more efficacious types of interventions are desired. Cruzain, identified as the major cathepsin for T. cruzi, plays a major role in the parasite's life cycle; making this enzyme very attractive for potential trypanocidal drugs discovery. The recombinant cruzain is synthesized as a zymogenic pro-protein (PCZN) which possesses a pro domain and a catalytic domain. In this …


The Characterization Of A Recombinant Virophage Integrase, Martin Christopher Chacon Jan 2016

The Characterization Of A Recombinant Virophage Integrase, Martin Christopher Chacon

Open Access Theses & Dissertations

Virophages are satellite-like dsDNA viruses that parasitize giant viruses of the family Mimiviridae. Mavirus is the second virophage discovered that associates with its host virus Cafeteria roenbergensis Virus (CroV). When co-infecting their common host cell Cafeteria roenbergensis, a marine zooplankton that is widely spread throughout the oceans, mavirus will inhibit CroV's replication. In addition, mavirus was shown to share high similarities to the Maverick/Polinton eukaryotic DNA transposons. A coding sequence in mavirus genome (MV02) reveals high homology to retroviral integrases such as those found in HIVs. The putative integrase MV02 is predicted to integrate mavirus DNA into the host genome. …


Study On Dioxygen Binding To Heme Using Scan Functional, Zegnet Yimer Muhammed Jan 2016

Study On Dioxygen Binding To Heme Using Scan Functional, Zegnet Yimer Muhammed

Open Access Theses & Dissertations

Density functional theory, a quantum mechanical based electronic structure method with GGA-PBE and MGG-SCAN functionals, are used to investigate the structure and energies of singlet, triplet, and quintet spin states of FeP (iron Porphyrin), FePIm (imidazole iron porphyrin), and FePImO2 (dioxygen imidazole iron porphyrin) systems. The binding and release of dioxygen to and from hemoglobin (Hb) are the most crucial reaction takes place in human body to sustain the existence of life. FePImO2 is used to model this phenomenon. When O2 binds to FePIm, the system undergoes a conformational change. i.e. from domed structure of FePIm in which the Fe …


Evaluation Of Small Molecules On The Excitatory Amino Acid Transporter 3 (Eaat3) For The Treatment Of Ocd, Emmanuel Zubia Jan 2015

Evaluation Of Small Molecules On The Excitatory Amino Acid Transporter 3 (Eaat3) For The Treatment Of Ocd, Emmanuel Zubia

Open Access Theses & Dissertations

We seek to discover new drug candidates for the excitatory amino acid transporter 3 (EAAT3) for the treatment of Obsessive Compulsive Disorder (OCD). We hypothesize that decreasing the glutamatergic transmission via EAAT3 intervention will create an amelioration of the symptoms of OCD. For this we have prepared in-silico binding calculations to identify a better compound that can stimulate EAAT3 and decrease glutamatergic transmission. This research will help us further understand and elucidate the role of glutamate in the neural mechanisms of this illness, which to date remain inconclusive. Those areas of study are significant because, until now, there is no …