A5051321476- Biochemical and Molecular Research
- Tuberculosis Research and Epidemiology
- Carbohydrate Chemistry and Synthesis
- Enzyme Structure and Function
- Mycobacterium research and diagnosis
- Glycosylation and Glycoproteins Research
- Bacterial Genetics and Biotechnology
- Bacteriophages and microbial interactions
- Monoclonal and Polyclonal Antibodies Research
- Helicobacter pylori-related gastroenterology studies
- RNA and protein synthesis mechanisms
- Enzyme Production and Characterization
- RNA Interference and Gene Delivery
- Chromosomal and Genetic Variations
- Viral Infections and Immunology Research
- Microbial Metabolic Engineering and Bioproduction
- Virus-based gene therapy research
- Microbial Natural Products and Biosynthesis
- Chemical Synthesis and Analysis
- DNA Repair Mechanisms
- Pneumocystis jirovecii pneumonia detection and treatment
- Antibiotic Resistance in Bacteria
- Advancements in Photolithography Techniques
- Polyamine Metabolism and Applications
- Amino Acid Enzymes and Metabolism
University of Nebraska Medical Center
2020-2025
Nebraska Medical Center
2020-2024
University of Toledo
2009-2019
Division of Chemistry
2016
University Surgical Associates
2015
National Institutes of Health
2003-2008
National Institute of Diabetes and Digestive and Kidney Diseases
2002-2008
Texas A&M University
1999-2005
Lawrence Livermore National Laboratory
2005
Howard Hughes Medical Institute
2003
DNA extraction represents a significant bottleneck in nucleic acid analysis. In this study, hydrophobic magnetic ionic liquids (MILs) were synthesized and employed as solvents for the rapid efficient of from aqueous solution. The DNA-enriched microdroplets manipulated by application field. three MILs examined study exhibited unique capabilities when applied toward variety samples matrices. High efficiencies obtained smaller single-stranded double-stranded using benzyltrioctylammonium...
In bacteria, the majority of exported proteins are translocated by Sec system, which recognizes signal sequence a preprotein and uses ATP proton motive force to mediate protein translocation across cytoplasmic membrane. SecA is an essential component this containing molecular motor that facilitates translocation. Here we report three-dimensional structure Mycobacterium tuberculosis . Each subunit homodimer contains “motor” domain domain. The predicts can interact with SecYEG pore function as...
Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), is the leading cause of death worldwide infectious disease. Treatment Mtb infection requires a six-month course multiple antibiotics, an extremely challenging regimen necessitated Mtb's ability to form drug-tolerant persister cells. formation dependent on trehalose catalytic shift, stress-responsive metabolic remodeling mechanism in which disaccharide liberated from cell surface glycolipids and repurposed as internal carbon...
The maintenance of the highly hydrophobic cell wall is central to survival Mycobacterium tuberculosis within its host environment. antigen 85 proteins (85A, 85B, and 85C) M. help maintain integrity 1) by catalyzing transfer mycolic acids arabinogalactan 2) through synthesis trehalose dimycolate (cord factor). Additionally, these secreted allow for rapid invasion alveolar macrophages via direct interactions between immune system invading bacillus. Here we describe two crystal structures:...
Isoxyl and Thiacetazone are two antitubercular prodrugs formerly used in the clinical treatment of tuberculosis. Although both have recently been shown to kill Mycobacterium tuberculosis through inhibition dehydration step type II fatty acid synthase pathway, their detailed mechanism inhibition, precise number enzymes involved activation nature activated forms remained unknown. We here demonstrate that specifically covalently react with a cysteine residue (Cys61) HadA subunit dehydratase...
The unique cell wall of mycobacteria is essential to their viability and the target many clinically used anti-tuberculosis drugs inhibitors under development. Despite intensive efforts identify ligase(s) responsible for covalent attachment two major heteropolysaccharides mycobacterial wall, arabinogalactan (AG) peptidoglycan (PG), enzyme or enzymes have remained elusive. We here report on identification Mycobacterium tuberculosis, CpsA1 (Rv3267) CpsA2 (Rv3484), this function. belong...
2-Alkyl-1,2-benzisoselenazol-3(2H)-ones, represented by ebselen (1a), are being studied intensively for a range of medicinal applications. We describe both new thermal and photoinduced copper-mediated cross-coupling between potassium selenocyanate (KSeCN) N-substituted ortho-halobenzamides to form 2-alkyl-1,2-benzisoselenazol-3(2H)-ones containing C–Se–N bond. The copper ligand (1,10-phenanthroline) facilitates C–Se bond formation during heating via mechanism that likely involves atom...
New 2-aminothiophenes (2AT) were identified with MICs = 0.23–0.44 μM against drug sensitive and resistant strains of<italic>Mycobacterium tuberculosis</italic>.
The antibacterial agent Bio-AMS is metabolized in vivo through hydrolysis of the central acyl-sulfamide linker leading to high clearance and release a moderately cytotoxic metabolite M1. Herein, we disclose analogues designed prevent metabolism moiety steric hindrance or attenuation electrophilicity. Bio-9 was identified as metabolically stable analogue with single-digit nanomolar dissociation constant for biotin protein ligase (BPL) minimum inhibitory concentrations (MICs) against...
Targeting cell wall biosynthesis is an established target for developing drugs that treat bacterial infections. The enzymes in the pathways are lacking humans, making these targets more selective bacteria. D-cycloserine (DCS) has been studied years as antibiotic targeting peptidoglycan of various bacteria and used a second-line drug to multi-drug resistance tuberculosis. Still, its usage limited due toxicity narrow therapeutic window, which exemplified by high DCS tolerance exhibited...
The rise of multidrug-resistant and totally drug-resistant tuberculosis the association with an increasing number HIV-positive patients developing emphasize necessity to find new antitubercular targets drugs. antigen 85 (Ag85) complex from Mycobacterium plays important roles in biosynthesis major components mycobacterial cell envelope. For this reason, Ag85 has emerged as attractive drug target. Recently, ebselen was identified effective inhibitor through covalent modification a cysteine...
The mycobacterial outer membrane, or mycomembrane, is essential for the viability and virulence of Mycobacterium tuberculosis related pathogens. mycomembrane a dynamic structure, whose chemical composition biophysical properties can change during stress to give an advantage bacterium. However, mechanisms that govern remodeling their significance pathogenesis are still not well characterized. Recent studies have shown trehalose dimycolate (TDM), major glycolipid broken down by...