Identification of Anticryptococcal Bornyl Compounds from Verbesina turbacensis and Their Structure-Activity Relationships.

is an opportunistic fungal pathogen that has limited treatment options. Natural product plant extracts offer a cost-effective option for the discovery of new anticryptococcal lead compounds. The acetone bark extract of was found to potently inhibit and was subjected to bioautography.

Natural Product Inhibition and Enzyme Kinetics Related to Phylogenetic Characterization for Bacterial Peptidyl-tRNA Hydrolase 1.

With the relentless development of drug resistance and re-emergence of many pathogenic bacteria, the need for new antibiotics and new antibiotic targets is urgent and growing. Bacterial peptidyl-tRNA hydrolase, Pth1, is emerging as a promising new target for antibiotic development. From the conserved core and high degree of structural similarity, broad-spectrum inhibition is postulated.

Bicelles Rich in both Sphingolipids and Cholesterol and Their Use in Studies of Membrane Proteins.

How the distinctive lipid composition of mammalian plasma membranes impacts membrane protein structure is largely unexplored, partly because of the dearth of isotropic model membrane systems that contain abundant sphingolipids and cholesterol. This gap is addressed by showing that phingomyelin and hlesterol-ich (SCOR) lipid mixtures with phosphatidylcholine can be cosolubilized by -dodecyl-β-melibioside to form bicelles. Small-angle X-ray and neutron scattering, as well as cryo-electron microscopy, demonstrate that these assemblies are stable over a wide range of conditions and exhibit the bilayered-disc morphology of ideal bicelles even at low lipid-to-detergent mole ratios.

Structure and physiological function of the human KCNQ1 channel voltage sensor intermediate state.

Voltage-gated ion channels feature voltage sensor domains (VSDs) that exist in three distinct conformations during activation: resting, intermediate, and activated. Experimental determination of the structure of a potassium channel VSD in the intermediate state has previously proven elusive. Here, we report and validate the experimental three-dimensional structure of the human KCNQ1 voltage-gated potassium channel VSD in the intermediate state.

Volatile Compositions and Antifungal Activities of Native American Medicinal Plants: Focus on the Asteraceae.

In the past, Native Americans of North America had an abundant traditional herbal legacy for treating illnesses, disorders, and wounds. Unfortunately, much of the ethnopharmacological knowledge of North American Indians has been lost due to population destruction and displacement from their native lands by European-based settlers. However, there are some sources of Native American ethnobotany remaining.

Bigger Data Approach to Analysis of Essential Oils and Their Antifungal Activity against , , and .

With increasing drug resistance and the poor state of current antifungals, the need for new antifungals is urgent and growing. Therefore, we tested a variety of essential oils for antifungal activity. We report the minimum inhibitory concentrations (MIC) values for a common set of 82 essential oils against , , and .

Improving the accuracy and resolution of neutron crystallographic data by three-dimensional profile fitting of Bragg peaks in reciprocal space.

Neutron crystallography is a powerful technique for directly visualizing the locations of H atoms in biological macromolecules. This information has provided key new insights into enzyme mechanisms, ligand binding and hydration. However, despite the importance of this information, the application of neutron crystallography in biology has been limited by the relatively low flux of available neutron beams and the large incoherent neutron scattering from hydrogen, both of which contribute to weak diffraction data with relatively low signal-to-background ratios.

Antifungal and Cytotoxic Activities of Sixty Commercially-Available Essential Oils.

There is an urgent and unmet need for new antifungal therapies. Global fungal infection rates continue to rise and fungal infections pose increasing burdens on global healthcare systems. Exacerbating the situation, the available antifungal therapeutic arsenal is limited and development of new antifungals has been slow.

Chemical Composition, Enantiomeric Distribution, and Antifungal Activity of the Oleoresin Essential Oil of Protium amazonicum from Ecuador.

species (Burseraceae) have been used in the treatment of various diseases and conditions such as ulcers and wounds. The essential oil from the oleoresin of was obtained by hydrodistillation and analyzed by GC-MS, GC-FID, and chiral GC-MS. oleoresin oil was screened for antifungal activity against , , and .

Novel Antifungal Activity for the Lectin Scytovirin: Inhibition of and .

Pathogenic cryptococci are encapsulated yeast that can cause severe meningoencephalitis. Existing therapeutic options are dated and there is a growing need for new alternative antifungal agents for these fungi. Here we report novel inhibition of pathogenic cryptococci by the antimicrobial lectin Scytovirin.

Structural and biochemical differences between the Notch and the amyloid precursor protein transmembrane domains.

γ-Secretase cleavage of the Notch receptor transmembrane domain is a critical signaling event for various cellular processes. Efforts to develop inhibitors of γ-secretase cleavage of the amyloid-β precursor C99 protein as potential Alzheimer's disease therapeutics have been confounded by toxicity resulting from the inhibition of normal cleavage of Notch. We present biochemical and structural data for the combined transmembrane and juxtamembrane Notch domains (Notch-TMD) that illuminate Notch signaling and that can be compared and contrasted with the corresponding traits of C99.

Chemotypic Characterization and Biological Activity of Rosmarinus officinalis.

Rosemary ( L.) is a popular herb in cooking, traditional healing, and aromatherapy. The essential oils of were obtained from plants growing in Victoria (Australia), Alabama (USA), Western Cape (South Africa), Kenya, Nepal, and Yemen.

Essential Oil Characterization of Thymus vulgaris from Various Geographical Locations.

Thyme ( L.) is a commonly used flavoring agent and medicinal herb. Several chemotypes of thyme, based on essential oil compositions, have been established, including (1) linalool; (2) borneol; (3) geraniol; (4) sabinene hydrate; (5) thymol; (6) carvacrol, as well as a number of multiple-component chemotypes.

Expedited isolation of natural product peptidyl-tRNA hydrolase inhibitors from a Pth1 affinity column.

New antibiotics and new antibiotic targets are needed to counter the development of bacterial drug resistance that threatens to return the human population to the pre-antibiotic era. Bacterial peptidyl-tRNA hydrolase (Pth1) is a promising new antibiotic target in the early stages of development. While inhibitory activity has been observed in a variety of natural products, bioactive fractionation has been a bottleneck for inhibitor isolation.

Bacterial production of site specific C labeled phenylalanine and methodology for high level incorporation into bacterially expressed recombinant proteins.

Nuclear magnetic resonance spectroscopy studies of ever larger systems have benefited from many different forms of isotope labeling, in particular, site specific isotopic labeling. Site specific C labeling of methyl groups has become an established means of probing systems not amenable to traditional methodology. However useful, methyl reporter sites can be limited in number and/or location.

α-Pyrone derivatives, tetra/hexahydroxanthones, and cyclodepsipeptides from two freshwater fungi.

Eighteen (1-18) and seven (1, 4, 6-8, 17 and 18) compounds were isolated from organic extracts of axenic cultures of two freshwater fungi Clohesyomyces sp. and Clohesyomyces aquaticus (Dothideomycetes, Ascomycota), respectively. Compounds 1-12 belong to the α-pyrone class of natural products, compounds 13 and 14 were tetrahydroxanthones, compounds 15 and 16 were hexahydroxanthones, while compounds 17 and 18 were cyclodepsipeptides.

Expression, purification, and buffer solubility optimization of the putative human peptidyl-tRNA hydrolase PTRHD1.

Performing the essential function of recycling peptidyl-tRNAs, peptidyl-tRNA hydrolases are ubiquitous in all domains of life. The multicomponent eukaryotic Pth system differs greatly from the bacterial system composed predominantly of a single Pth1 enzyme. While bacterial Pth1s are structurally well characterized and promising new targets for antibiotic development, eukaryotic Pths are largely understudied.

Small Molecule Docking Supports Broad and Narrow Spectrum Potential for the Inhibition of the Novel Antibiotic Target Bacterial Pth1.

Peptidyl-tRNA hydrolases (Pths) play ancillary yet essential roles in protein biosynthesis by recycling peptidyl-tRNA. In E. coli, inhibition of bacterial Pth1 leads to accumulation of peptidyl-tRNA, depletion of aminoacyl-tRNA, and cell death.

Neutron diffraction analysis of Pseudomonas aeruginosa peptidyl-tRNA hydrolase 1.

Perdeuterated peptidyl-tRNA hydrolase 1 from Pseudomonas aeruginosa was crystallized for structural analysis using neutron diffraction. Crystals of perdeuterated protein were grown to 0.15 mm(3) in size using batch crystallization in 22.

Commercial Scale Cucumber Fermentations Brined with Calcium Chloride Instead of Sodium Chloride.

Development of low salt cucumber fermentation processes present opportunities to reduce the amount of sodium chloride (NaCl) that reaches fresh water streams from industrial activities. The objective of this research was to translate cucumber fermentation brined with calcium chloride (CaCl2 ) instead of NaCl to commercial scale production. Although CaCl2 brined cucumber fermentations were stable in laboratory experiments, commercial scale trials using 6440 L open-top tanks rapidly underwent secondary cucumber fermentation.

Metabolic footprinting of Lactobacillus buchneri strain LA1147 during anaerobic spoilage of fermented cucumbers.

Lactobacillus buchneri has recently been associated with anaerobic spoilage of fermented cucumbers due to its ability to metabolize lactic acid into acetic acid and 1,2-propanediol. However, we have limited knowledge of other chemical components in fermented cucumber that may be related to spoilage and the unique metabolic capabilities of L. buchneri.

Antifungal activity of plant extracts against Aspergillus niger and Rhizopus stolonifer.

Despite recent advances in antifungal development, fungi remain a devastating threat to human health and compromise viability of the food supply. Plant based antimicrobials represent a vast untapped source with tremendous potential. Herein we present the antifungal properties of more than 50 plant extracts against two important human and agricultural pathogens, Aspergillus niger and Rhizopus stolonifer.

Recombinant production, crystallization and X-ray crystallographic structure determination of peptidyl-tRNA hydrolase from Salmonella typhimurium.

Peptidyl-tRNA hydrolase (Pth; EC 3.1.1.

Expression, purification, and solubility optimization of peptidyl-tRNA hydrolase 1 from Bacillus cereus.

Peptidyl-tRNA hydrolase 1 cleaves the ester bond of peptidyl-tRNA thereby recycling peptidyl-tRNAs generated from premature termination of translation and expression of minigenes and short ORFs. Bacterial Pth1 is essential, highly conserved, and has no essential eukaryotic homolog making it a good target for antibacterial development. Herein we describe the cloning of pth1 gene from Bacillus cereus as an N-terminal hexahistidine fusion protein.

Small molecule binding, docking, and characterization of the interaction between Pth1 and peptidyl-tRNA.

Bacterial Pth1 is essential for viability. Pth1 cleaves the ester bond between the peptide and nucleotide of peptidyl-tRNA generated from aborted translation, expression of mini-genes, and short ORFs. We have determined the shape of the Pth1:peptidyl-tRNA complex using small angle neutron scattering.