Biochemistry Commons^™

Mutational Analysis Of The Nitrogenase Carbon Monoxide Protective Protein Cown Reveals That A Conserved C‑Terminal Glutamic Acid Residue Is Necessary For Its Activity, Dustin L. Willard, Joshuah J. Arellano, Mitch Underdahl, Terrence M. Lee, Avinash S. Ramaswamy, Gabriella Fumes, Agatha Kliman, Emily Y. Wong, Cedric P. Owens

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Nitrogenase is the only enzyme that catalyzes the reduction of nitrogen gas into ammonia. Nitrogenase is tightly inhibited by the environmental gas carbon monoxide (CO). Many nitrogen fixing bacteria protect nitrogenase from CO inhibition using the protective protein CowN. This work demonstrates that a conserved glutamic acid residue near the C-terminus of Gluconacetobacter diazotrophicus CowN is necessary for its function. Mutation of the glutamic acid residue abolishes both CowN’s protection against CO inhibition and the ability of CowN to bind to nitrogenase. In contrast, a conserved C-terminal cysteine residue is not important for CO protection by CowN. Overall, this work …

Predicted Structure And Analysis Of The Glycoprotein From Sars-Cov-2 Variants Of Interest, Boris Shabaltiy

Honors Theses

SARS-CoV-2 has had a devastating effect on the world, and while the public concern and severity of the diseased caused by it have decreased, it is still crucial to monitor the virus for mutations so we can rapidly identify new variants of concern, and then rapidly prepare new vaccines and treatments. The SARS-CoV-2 spike (S) protein from the first isolates of the virus (root variant) was structurally characterized in early 2021. The spike protein structure, designated 7CZW, was uploaded to RCSB Protein Data Bank (RCSB PDB). All subsequent mutations the S protein has accumulated are based on the amino acid …

Elucidating The Impact Of Sos-Response Timing In On Escherichia Coli Survival Following Treatment With Fluoroquinolone Topoisomerase Inhibitors, Stephanie Schofield

Honors Scholar Theses

Antibiotic treatment failure is a public health crisis, with a 2019 report stating that roughly 35,000 deaths occur in the United States yearly due to bacterial infections that are unresponsive to antibiotics (1). One complication in the treatment of bacterial infection is antibiotic persistence which further compromises our battle to effectively treat infection. Bacterial persisters can exist in clonal bacterial cultures and can tolerate antibiotic treatment by undergoing reversible phenotypic changes. They can survive drug concentrations that their genetically identical kin cannot. Some persisters remain in a slow growing state and are difficult to target with current antibiotics. A specific …

Botanical Assessment Of Remnant Floodplain Habitats Along Plaster Creek, Kent County, Michigan: Assessing Changes Since The 1890s, Haley R. Weesies, Garrett Crow, David Warners

Faculty and Professional Research

Plaster Creek, a tributary of the Grand River, drains a 58-square mile watershed in Kent County, Michigan. Its headwaters originate in the agriculturally dominated southwestern portion of the county, and then it meanders through residential, commercial, and urban areas of Kentwood and Grand Rapids before it empties into the Grand River about one mile south of downtown Grand Rapids. Much of Plaster Creek’s original floodplain, like the rest of its watershed, has been drastically altered and degraded over time due to the development of residential neighborhoods, commercial properties, agriculture, and industrial zones. Floodplains house unique assemblages of Michigan’s native biodiversity …

Methanogen Metabolic Flexibility, Sean Carr

School of Biological Sciences: Dissertations, Theses, and Student Research

Methanogens are obligately anaerobic archaea which produce methane as a byproduct of their respiration. They are found across a wide diversity of environments and play an important role in cycling carbon in anaerobic spaces and the removal of harmful fermentation byproducts which would otherwise inhibit other organisms. Methanogens subsist on low-energy substrates which requires them to utilize a highly efficient central metabolism which greatly favors respiratory byproducts over biomass. This metabolic strategy creates high substrate:product conversion ratios which is industrially relevant for the production of biomethane, but may also allow for the production of value-added commodities. Particularly of interest are …

Increasing The Resilience Of Plant Immunity To A Warming Climate, Jong Hum Kim, Christian Castroverde, Shuai Huang, Chao Li, Richard Hilleary, Adam Seroka, Reza Sohrabi, Diana Medina-Yerena, Bethany Huot, Jie Wang, Sharon Marr, Mary Wildermuth, Tao Chen, John Macmicking, Sheng Yang He

Biology Faculty Publications

Extreme weather conditions associated with climate change affect many aspects of plant and animal life, including the response to infectious diseases. Production of salicylic acid (SA), a central plant defence hormone, is particularly vulnerable to suppression by short periods of hot weather above the normal plant growth temperature range via an unknown mechanism. Here we show that suppression of SA production in Arabidopsis thaliana at 28 °C is independent of PHYTOCHROME B (phyB) and EARLY FLOWERING 3 (ELF3), which regulate thermo-responsive plant growth and development. Instead, we found that formation of GUANYLATE BINDING PROTEIN-LIKE 3 (GBPL3) defence-activated biomolecular condensates (GDACs) …

An Investigation To Corroborate Volatile And Biological Profiles Of Human Odor For Forensic Subject Identification, Chantrell J.G. Frazier

FIU Electronic Theses and Dissertations

Hands are an integral part in transferring complex microbial communities to and from our surroundings. As a result, hands are significant in provenance investigations as specific microbiota can be deposited on everyday objects through touch interactions. Skin microbiome, including bacteria, fungi, and viruses, are unique to each person, and this ‘uniqueness’ can be exploited and applied to forensic identification. Skin microbiota and volatile organic compounds (VOCs) are closely related due to specific bacteria breaking down non-volatile organic compounds to volatile organic compounds that are characteristically present in human scent. However, analyses of microbiota from touch interactions have proven to be …

Escherichia Coli Alanyl-Trna Synthetase Maintains Proofreading Activity And Translational Accuracy Under Oxidative Stress, Arundhati Kavoor, Paul Kelly, Michael Ibba

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Aminoacyl-tRNA synthetases (aaRSs) are enzymes that synthesize aminoacyl-tRNAs to facilitate translation of the genetic code. Quality control by aaRS proofreading and other mechanisms maintains translational accuracy, which promotes cellular viability. Systematic disruption of proofreading, as recently demonstrated for alanyl-tRNA synthetase (AlaRS), leads to dysregulation of the proteome and reduced viability. Recent studies showed that environmental challenges such as exposure to reactive oxygen species can also alter aaRS synthetic and proofreading functions, prompting us to investigate if oxidation might positively or negatively affect AlaRS activity. We found that while oxidation leads to modification of several residues in Escherichia coli AlaRS, unlike …

Characterizing The Amino Acid Activation Center Of The Naturally Editing-Deficient Aminoacyl-Trna Synthetase Phers In Mycoplasma Mobile, Nien-Ching Han, Arundhati Kavoor, Michael Ibba

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

To ensure correct amino acids are incorporated during protein synthesis, aminoacyl-tRNA synthetases (aaRSs) employ proofreading mechanisms collectively referred to as editing. Although editing is important for viability, editing-deficient aaRSs have been identified in host-dependent organisms. In Mycoplasma mobile, editing-deficient PheRS and LeuRS have been identified. We characterized the amino acid activation site of MmPheRS and identified a previously unknown hyperaccurate mutation, L287F. Additionally, we report that m-Tyr, an oxidation byproduct of Phe which is toxic to editing-deficient cells, is poorly discriminated by MmPheRS activation and is not subjected to editing. Furthermore, expressing MmPheRS and the hyperaccurate variants renders …

Botanical Inventory And Management Consideration For Potential Park At 32 Nd Street Property: City Of Grand Rapids Parks And Recreation, David Warners, William Hofmann, Hayden Janssen, Martin Vanderschoot, Garrett Crow

Faculty and Professional Research

During the spring and summer of 2022, a botanical inventory and floristic quality assessment was carried out by Calvin University students and faculty for the 32 nd Street Property proposed as a 17-acre potential City Park, located at 2163 32 nd Street SE in Grand Rapids, Michigan. The purpose of this inventory was to inform the staff of the Grand Rapids Parks and Recreation Department of the botanical significance of this newly sectioned property and also to provide information for the City to share with neighbors of the plants that could be found in this parcel. The research conducted as …

Copper(Ii) And Silver(I)‑1,10‑Phenanthroline‑5,6‑Dione Complexes Interact With Double‑Stranded Dna: Further Evidence Of Their Apparent Multi‑Modal Activity Towards Pseudomonas Aeruginosa, Anna Clara Milesi Galdino, Lívia Viganor, Matheus Mendonça Pereira, Michael Devereux, Malachy Mccann, Marta Helena Branquinha, Zara Molphy, Sinéad O'Carroll, Conor Bain, Georgia Menounou, Andrew Kellett, André Luis Souza Dos Santos

Articles

Tackling microbial resistance requires continuous efforts for the development of new molecules with novel mechanisms of action and potent antimicrobial activity. Our group has previously identified metal-based compounds, [Ag(1,10-phenanthroline-5,6-dione)2]ClO4 (Ag-phendione) and [Cu(1,10-phenanthroline-5,6-dione)3](ClO4)2.4H2O (Cu-phendione), with efficient antimicrobial action against multidrug-resistant species. Herein, we investigated the ability of Ag-phendione and Cu-phendione to bind with double-stranded DNA using a combination of in silico and in vitro approaches. Molecular docking revealed that both phendione derivatives can interact with the DNA by hydrogen bonding, hydrophobic and electrostatic interactions. Cu-phendione exhibited the highest binding affinity to either major (− 7.9 kcal/mol) or minor (− 7.2 kcal/mol) …

Microbial Labilization And Diversification Of Pyrogenic Dissolved Organic Matter, Aleksandar I. Goranov, Andrew S. Wozniak, Kyle W. Bostick, Andrew R. Zimmerman, Siddhartha Mitra, Patrick G. Hatcher

Chemistry & Biochemistry Faculty Publications

With the increased occurrence of wildfires around the world, interest in the chemistry of pyrogenic organic matter (pyOM) and its fate in the environment has increased. Upon leaching from soils by rain events, significant amounts of dissolved pyOM (pyDOM) enter the aquatic environment and interact with microbial communities that are essential for cycling organic matter within the different biogeochemical cycles. To evaluate the biodegradability of pyDOM, aqueous extracts of laboratory-produced biochars were incubated with soil microbes, and the molecular changes to the composition of pyDOM were probed using ultrahigh-resolution mass spectrometry (Fourier transform–ion cyclotron resonance–mass spectrometry). Given that solar irradiation …

High-Resolution Cryo-Electron Microscopy Structure Of Photosystem Ii From The Mesophilic Cyanobacterium, Synechocystis Sp. Pcc 6803, Christopher J. Gisriel, Jimin Wang, Jinchan Liu, David A. Flesher, Krystle M. Reiss, Hao-Li Huang, Ke R. Yang, William H. Armstrong, M. R. Gunner, Victor S. Batista, Richard J. Debus, Gary W. Brudvig

Publications and Research

Photosystem II (PSII) enables global-scale, light-driven water oxidation. Genetic manipulation of PSII from the mesophilic cyanobacterium Synechocystis sp. PCC 6803 has provided insights into the mechanism of water oxidation; however, the lack of a highresolution structure of oxygen-evolving PSII from this organism has limited the interpretation of biophysical data to models based on structures of thermophilic cyanobacterial PSII. Here, we report the cryo-electron microscopy structure of PSII from Synechocystis sp. PCC 6803 at 1.93-Å resolution. A number of differences are observed relative to thermophilic PSII structures, including the following: the extrinsic subunit PsbQ is maintained, the C terminus of the …

A Conserved Structural Role For The Walker-A Lysine In P-Loop Containing Kinases, Fatlum Hajredini, Ranajeet Ghose

Publications and Research

Bacterial tyrosine kinases (BY-kinases) and shikimate kinases (SKs) comprise two structurally divergent P-loop containing enzyme families that share similar catalytic site geometries, most notably with respect to their Walker-A, Walker-B, and DxD motifs. We had previously demonstrated that in BY-kinases, a specific interaction between the Walker-A and Walker-B motifs, driven by the conserved “catalytic” lysine housed on the former, leads to a conformation that is unable to efficiently coordinate Mg²⁺•ATP and is therefore incapable of chemistry. Here, using enhanced sampling molecular dynamics simulations, we demonstrate that structurally similar interactions between the Walker-A and Walker-B motifs, also mediated by …

Oxidation Alters The Architecture Of The Phenylalanyl-Trna Synthetase Editing Domain To Confer Hyperaccuracy, Pooja Srinivas, Rebecca E. Steiner, Ian J. Pavelich, Ricardo Guerrera-Ferreira, Puneet Juneja, Michael Ibba, Christine M. Dunham

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

High fidelity during protein synthesis is accomplished by aminoacyl-tRNA synthetases (aaRSs). These enzymes ligate an amino acid to a cognate tRNA and have proofreading and editing capabilities that ensure high fidelity. Phenylalanyl-tRNA synthetase (PheRS) preferentially ligates a phenylalanine to a tRNA^Phe over the chemically similar tyrosine, which differs from phenylalanine by a single hydroxyl group. In bacteria that undergo exposure to oxidative stress such as Salmonella enterica serovar Typhimurium, tyrosine isomer levels increase due to phenylalanine oxidation. Several residues are oxidized in PheRS and contribute to hyperactive editing, including against mischarged Tyr-tRNA^Phe, despite these oxidized residues not …

Finding The Balance​ The Effects Of Α-Cyclodextrin, 2-Hydroxypropyl-Β-Cyclodextrin, And Cholesterol Bacteroides Vulgatus And Clostridium Bolteae​, Bethany Weaver

Honors Program Projects

Atherosclerosis is a cardiovascular disease that is characterized by the hardening of arteries through the formation of cholesterol plaques. Cyclodextrins could potentially treat atherosclerosis by shrinking plaques. These cyclic oligosaccharides can make complexes with cholesterol but have also shown toxic side effects. This study looked for potential negative effects of cyclodextrins and cholesterol on gut bacteria. It was hypothesized that Bacteroides vulgatus will have decreased growth when grown in broth with cholesterol. In contrast, Clostridium bolteae will have decreased growth when grown in broth with cyclodextrins. Due to the fact that these bacteria are anaerobic, Clostridium bolteae and Bacteroides vulgatus, …

Toward The Discovery Of Biological Functions Associated With The Mechanosensor Mtl1p Of Saccharomyces Cerevisiae Via Integrative Multi-Omics Analysis, Nelson Martínez-Matías, Nataliya Chorna, Sahily González-Crespo, Lilliam Villanueva, Ingrid Montes-Rodríguez, Loyda M. Melendez-Aponte, Abiel Roche-Lima, Kelvin Carrasquillo-Carrión, Ednalise Santiago-Cartagena, Brian C. Rymond, Mohan Babu, Igor Stagljar, José R. Rodríguez-Medina

Biology Faculty Publications

Functional analysis of the Mtl1 protein in Saccharomyces cerevisiae has revealed that this transmembrane sensor endows yeast cells with resistance to oxidative stress through a signaling mechanism called the cell wall integrity pathway (CWI). We observed upregulation of multiple heat shock proteins (HSPs), proteins associated with the formation of stress granules, and the phosphatase subunit of trehalose 6-phosphate synthase which suggests that mtl1Δ strains undergo intrinsic activation of a non-lethal heat stress response. Furthermore, quantitative global proteomic analysis conducted on TMT-labeled proteins combined with metabolome analysis revealed that mtl1Δ strains exhibit decreased levels of metabolites of carboxylic acid metabolism, decreased …

Covid19 Disease Map, A Computational Knowledge Repository Of Virus–Host Interaction Mechanisms, Marek Ostaszewski, Tomáš Helikar, Bhanwar Lal Puniya, A Host Of Co-Authors, Covid-19 Disease Map Community

Department of Biochemistry: Faculty Publications

We need to effectively combine the knowledge from surging literature with complex datasets to propose mechanistic models of SARS-CoV-2 infection, improving data interpretation and predicting key targets of intervention. Here, we describe a large-scale community effort to build an open access, interoperable and computable repository of COVID-19 molecular mechanisms. The COVID-19 Disease Map (C19DMap) is a graphical, interactive representation of disease-relevant molecular mechanisms linking many knowledge sources. Notably, it is a computational resource for graph-based analyses and disease modelling. To this end, we established a framework of tools, platforms and guidelines necessary for a multifaceted community of biocurators, domain experts, …

Plaster Creek Floodplain And Adjacent Ravines Near Stanaback Park: Botanical Inventory Highlights And Management Considerations, David Warners, Garrett Crow, Haley Weesies

Faculty and Professional Research

In the summer of 2021, the research team visited this area of ravines and floodplain a total of twenty-one times to conduct our field research. During the visits, they carefully walked throughout different sections of the study site, identifying each vascular plant species they saw growing there and observing how the flora developed throughout the season. In addition to keeping detailed field notes, they documented permanent records of the findings of our inventory by collecting voucher specimens that have been deposited in the Calvin University Herbarium. Additionally, they sent duplicate specimens to the Michigan State University Herbarium and/or University of …

Botanical Inventory Highlights And Management Considerations For Covenant Park, David Warners, Garrett Crow, Haley Weesies

Faculty and Professional Research

In the spring and summer of 2021, Calvin University students and faculty conducted a botanical inventory and assessment of the natural areas in Covenant Park, located at 3724 Shaffer Avenue SE, Kentwood, MI 49512. Given that the property was recently acquired by the City of Kentwood Parks & Recreation, the purpose of this inventory is to inform Kentwood Parks and Recreation staff about the site’s floristic quality, diversity, and ecological significance. The specific objectives of this study are to 1) provide a comprehensive inventory of the species of plants occurring on the property, 2) identify particular areas that would benefit …

Bacterial Mechanisms Of Toxicity And Resistance To Organoarsenicals, Luis D. Garbinski

FIU Electronic Theses and Dissertations

Arsenic is a toxic element prevalent in the environment since the origin of life on Earth. Bacteria evolved in an arsenic-rich environment, where they developed ways to both overcome arsenic toxicity and harness it to compete with other organisms. These mechanisms include chemical modifications (e.g. oxidation, methylation), degradation, and efflux. The goal of this dissertation is to better characterize these mechanisms, illuminating the arsenic biogeocycle and allowing us to harness organoarsenical toxicity for novel antibiotics. A goal of my research was to elucidate the antibiotic properties of MAs(III), which is synthesized by bacteria to thrive over other bacteria, by identifying …

Analysis And Exploration Of Novel Antibiotic-Producing Streptomyces Spp. In Spokane County, Washington, Kyle S. Kramer, Jenifer B. Walke Ph.D

2020 Symposium Posters

According to the Centers for Disease Control and Prevention, a US citizen is infected by an antibiotic-resistant pathogen every 11 seconds, and every 15 minutes, a patient dies as a result of these infections. Due to the increasing incidence of antibiotic-resistant pathogenic microbes, the study and exploration of novel antibiotics from novel environments are imperative as infectious diseases are the second leading cause of death in the United States. The purpose of this research is to investigate and analyze antibiotic-producing soil microbes in Spokane County, WA, with hopes of discovering novel antibiotic-producing microbes, specifically Streptomyces species, and explore some of …

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

Department of Biochemistry: Dissertations, Theses, and Student Research

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

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

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

UCARE Research Products

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

Impact Of Metazooplankton Filter Feeding On Escherichia Coli Under Variable Environmental Conditions, Niveen S. Ismail, Brittney M. Blokker, Tyler R. Feeney, Ruby H. Kohn, Jingyi Liu, Vivian E. Nelson, Mariah C. Ollive, Sarah B. L. Price, Emma J. Underdaha

Engineering: Faculty Publications

The fecal indicator bacterial species Escherichia coli is an important measure of water quality and a leading cause of impaired surface waters. We investigated the impact of the filter-feeding metazooplankton Daphnia magna on the inactivation of E. coli. The E. coli clearance rates of these daphnids were calculated from a series of batch experiments conducted under variable environmental conditions. Batch system experiments of 24 to 48 h in duration were completed to test the impacts of bacterial concentration, organism density, temperature, and water type. The maximum clearance rate for adult D. magna organisms was 2 ml h1 organism1. Less than …

Deepep: A Deep Learning Framework For Identifying Essential Proteins, Min Zeng, Min Li, Fang-Xiang Wu, Yaohang Li, Yi Pan

Computer Science Faculty Publications

Background: Essential proteins are crucial for cellular life and thus, identification of essential proteins is an important topic and a challenging problem for researchers. Recently lots of computational approaches have been proposed to handle this problem. However, traditional centrality methods cannot fully represent the topological features of biological networks. In addition, identifying essential proteins is an imbalanced learning problem; but few current shallow machine learning-based methods are designed to handle the imbalanced characteristics. Results: We develop DeepEP based on a deep learning framework that uses the node2vec technique, multi-scale convolutional neural networks and a sampling technique to identify essential proteins. …

Acute Systemic Inflammatory Response To Lipopolysaccharide Stimulation In Pigs Divergently Selected For Residual Feed Intake, Haibo Liu, Kristina M. Feye, Yet T. Nguyen, Anoosh Rakhshandeh, Crystal L. Loving, Jack C. M. Sekkers, Nicholas K. Gabler, Christopher K. Tuggle

Mathematics & Statistics Faculty Publications

Background: It is unclear whether improving feed efficiency by selection for low residual feed intake (RFI) compromises pigs’ immunocompetence. Here, we aimed at investigating whether pig lines divergently selected for RFI had different inflammatory responses to lipopolysaccharide (LPS) exposure, regarding to clinical presentations and transcriptomic changes in peripheral blood cells.

Results: LPS injection induced acute systemic inflammation in both the low-RFI and high-RFI line (n = 8 per line). At 4 h post injection (hpi), the low-RFI line had a significantly lower (p= 0.0075) mean rectal temperature compared to the high-RFI line. However, no significant differences in complete blood count …

How A Cell Knows Where To Divide: Oscillation Of Mind In Vivo, Colby Ferreira

Senior Honors Projects

Over two-million people in the United States are infected by antibiotic resistant bacteria each year. Of this number 23,000 die from these infections and other complications. Due to this, novel antibiotic targets are constantly being investigated. One process in prokaryotes that holds promise is cellular division. Bacterial cells grow and reproduce using a series of proteins known as the cell division machinery. This machinery enables the division of the parental cell into two identical daughter cells. The cell division machinery is similar between bacterial taxa, making it an ideal target for new classes of antibiotics. Therefore, understanding the molecular mechanisms …

Distribution Of Dengue And Zika Virus Igg Immunoglobulin, Madison Smith, Awadalkareem Adam, Anuja Mathew

Senior Honors Projects

Introduction. Dengue Virus (DENV) and Zika Virus (ZIKV) are viruses that belong to the Flavivirus family. They are transmitted by the Aedes aegypti species of mosquitoes. Infection with DENV can result in no symptoms, mild symptoms which include fever, rash, and headache (dengue fever) or more severe symptoms which include hemorrhage, dengue hemorrhagic fever (DHF) and shock, dengue shock syndrome (DSS). ZIKV, until recently caused mild disease but an outbreak in Brazil was associated with fetal complications such as microcephaly or Guillain-Barré syndrome in adults. Due to the similarity between ZIKV and DENV, antibodies (Abs) generated in humans to these …

Mycobacterium Tuberculosis Inhibitors: Action And Resistance, Pamela K. Garcia-Moreno

FIU Electronic Theses and Dissertations

Tuberculosis, an infectious disease caused by Mycobacterium tuberculosis, has been a global health problem for years. The emergence of drug resistance in this organism generates the necessity of exploring novel targets and developing new drugs. Topoisomerases are enzymes found in all kingdoms of life responsible for overcoming the topological barriers encountered during essential cellular processes. The genomes of mycobacteria encode only one type IA topoisomerase (MtopI), which has been validated as a novel TB drug target. The goal of this study is to obtain new information on the mechanism and resistance of endogenous and synthetic inhibitors of MtopI.

Rv1495 is …