A5015756915- Toxoplasma gondii Research Studies
- Heat shock proteins research
- Photosynthetic Processes and Mechanisms
- Ubiquitin and proteasome pathways
- Autophagy in Disease and Therapy
- Genomics and Phylogenetic Studies
- Protein Structure and Dynamics
- Malaria Research and Control
- Research on Leishmaniasis Studies
- RNA and protein synthesis mechanisms
- HIV Research and Treatment
- thermodynamics and calorimetric analyses
- Endoplasmic Reticulum Stress and Disease
- Redox biology and oxidative stress
- Heme Oxygenase-1 and Carbon Monoxide
- Venomous Animal Envenomation and Studies
- Polysaccharides and Plant Cell Walls
- Agricultural pest management studies
- Proteins in Food Systems
- Microbial Natural Products and Biosynthesis
- Trypanosoma species research and implications
- Magnetic and Electromagnetic Effects
- Paraquat toxicity studies and treatments
- Insect Resistance and Genetics
- Cancer Mechanisms and Therapy
North Seattle College
2007-2024
Infectious Disease Research Institute
2016-2023
Center for Infectious Disease Research
2007-2018
Molina Center for Energy and the Environment
2007
University of Washington
2000-2005
Weatherford College
2000
Michigan State University
1994-2000
University of Arizona
1988-1995
University of Wisconsin–Madison
1990
Cell walls are crucial for development, signal transduction, and disease resistance in plants. made of cellulose, hemicelluloses, pectins. Xyloglucan (XG), the principal load-bearing hemicellulose dicotyledonous plants, has a terminal fucosyl residue. A 60-kilodalton fucosyltransferase (FTase) that adds this residue was purified from pea epicotyls. Peptide sequence information FTase allowed cloning homologous gene, AtFT1 , Arabidopsis . Antibodies raised against recombinant AtFTase...
Abstract Allene oxide synthase (AOS) and fatty acid hydroperoxide lyase (HPL) are plant-specific cytochrome P450s that commit hydroperoxides to different branches of oxylipin metabolism. Here we report the cloning characterization AOS (LeAOS) HPL (LeHPL) cDNAs from tomato (Lycopersicon esculentum). Functional expression inEscherichia coli showed LeAOS andLeHPL encode enzymes metabolize 13- but not 9-hydroperoxide derivatives C18 acids. was active against both...
Cytoplasmic members of the heat shock protein hsp70 family have recently been implicated in transport proteins to endoplasmic reticulum and mitochondria. In addition, other homologues found mitochondria and, at least for homologue, may be involved proper folding assembly newly transported proteins. Since chloroplasts are an important site plant cells, we were interested determining whether might located this organelle. By using immunoblotting techniques two antibody preparations against...
Toxoplasmosis is a disease of prominent health concern that caused by the protozoan parasite Toxoplasma gondii. Proliferation T. gondii dependent on its ability to invade host cells, which mediated in part calcium-dependent protein kinase 1 (CDPK1). We have developed ATP competitive inhibitors TgCDPK1 block invasion parasites into preventing their proliferation. The presence unique glycine gatekeeper residue permits selective inhibition enzyme over human kinases. These potent do not inhibit...
New therapies are needed for the treatment of toxoplasmosis, which is a disease caused by protozoan parasite Toxoplasma gondii. To this end, we previously developed potent and selective inhibitor (compound 1) gondii calcium-dependent protein kinase 1 (TgCDPK1) that possesses antitoxoplasmosis activity in vitro vivo. Unfortunately, has human ether-a-go-go-related gene (hERG) inhibitory activity, associated with long Q-T syndrome, consequently presents cardiotoxicity risk. Here, describe...
Plants synthesize several families of low molecular weight (LMW) heat shock proteins (HSPs) in response to elevated temperatures. We have characterized two cDNAs, HSP18.1 and HSP17.9, that encode members the class I family LMW HSPs from pea (Pisum sativum). In addition, we investigated expression these at mRNA protein levels during stress recovery. HSP17.9 are 82.1% identical amino acid level 80.8 92.9% other angiosperms. Heat experiments were performed using intact seedlings subjected a...
Summary Plants synthesize four classes of small heat shock proteins (sHSPs); two are targeted to the plastid and endoplasmic reticulum, respectively, found in cytoplasm. In this paper, we describe a new role for cytoplasmic HSPs maturing embryos developing seeds. The expression each class sHSPs was examined pea seeds grown under non‐stress conditions using Western Northern analysis. Class I II coordinately expressed embryo accumulate levels seen moderately heat‐stressed leaves. Their...
Diverse higher plant species synthesize low molecular weight (LMW) heat shock proteins (HSPs) which localize to chloroplasts. These are homologous LMW HSPs found in the cytoplasm of all eukaryotes, a class whose mode action is not understood. To obtain basic information concerning role chloroplast HSPs, we examined accumulation, stability, tissue specificity, and intra-chloroplast localization HSP21, major HSP pea. Intact pea plants were subjected stress conditions would be encountered...
ABSTRACT Toxoplasma gondii , which causes toxoplasmic encephalitis and birth defects, contains an essential chloroplast-related organelle to proteins are trafficked via the secretory system. This organelle, apicoplast, is bounded by multiple membranes. In this report we identify a novel apicoplast-associated thioredoxin family protein, ATrx1, predominantly soluble or peripherally associated with membranes, localizes primarily outer compartments of organelle. As such, it represents first...
Apicomplexan parasites possess a plastid-like organelle called the apicoplast. Most proteins in Toxoplasma gondii apicoplast are encoded nucleus and imported post-translationally. T. often have long N-terminal extension that directs protein to It can be modeled as bipartite targeting sequence contains signal plastid transit peptide. We identified two nuclearly predicted made fusions with green fluorescent study domains required for targeting. The 42 amino acids of ribosomal S9 secretion...
Pea microsomes contain an α-fucosyltransferase that incorporates fucose from GDP-fucose into xyloglucan, adding it preferentially to the 2-<i>O</i>-position of galactosyl residue closest reducing end repeating subunit. This enzyme was solubilized with detergent and purified by affinity chromatography on GDP-hexanolamine-agarose followed gel filtration. By utilizing peptide sequences obtained enzyme, a cDNA clone isolated encodes 565-amino acid protein predicted molecular mass 64 kDa shows...
The apicoplast is a relict plastid essential for viability of the apicomplexan parasites Toxoplasma and Plasmodium. It surrounded by multiple membranes that proteins, substrates metabolites must traverse. Little known about membrane much less their sorting mechanisms. We have identified two sets proteins are homologous to transport phosphosugars or derivatives. Members first set bear N-terminal extensions similar those target lumen. While gondii lacks this type translocator, extension from...
Apicomplexan parasites are global killers, being the causative agents of diseases like toxoplasmosis and malaria. These known to be hypersensitive redox imbalance, yet little is understood about cellular roles their various regulators. The apicoplast, an essential plastid organelle, a verified apicomplexan drug target. Nuclear-encoded apicoplast proteins traffic through ER multiple sub-compartments place function. We propose that thioredoxins contribute control protein trafficking function...
The apicoplast is a relict plastid found in many apicomplexans, including the pathogens Toxoplasma gondii and Plasmodium falciparum. Nucleus-encoded proteins enter ER, after cleavage of signal sequence, are routed to by virtue transit peptide, which subsequently removed. To assess mechanisms localization we examined stable transfectants T. for processing various GFP fusion proteins. fusions bearing targeting sequences targeted efficiently plastid, with no retention even when an ER...
The apicoplast is a secondary plastid found in Toxoplasma gondii , Plasmodium species and many other apicomplexan parasites. Although the essential to parasite survival, little known about protein constituents of four membranes surrounding organelle. Luminal proteins are directed endoplasmic reticulum (ER) by an N‐terminal signal sequence from there transit peptide domain. We have identified membrane‐associated AAA protease T. FtsH1. lacks canonical bipartite‐targeting sequence,...
We previously discovered compounds based on a 5-aminopyrazole-4-carboxamide scaffold to be potent and selective inhibitors of CDPK1 from T. gondii. The current work, through structure–activity relationship studies, led the discovery (34 35) with improved characteristics over starting inhibitor 1 in terms solubility, plasma exposure after oral administration mice, or efficacy parasite growth inhibition. Compounds 34 35 were further demonstrated more effective than mouse infection model...
Toxoplasma gondii and malaria parasites contain a unique essential relict plastid called the apicoplast. Most apicoplast proteins are encoded in nucleus transported to organelle via endoplasmic reticulum (ER). Three trafficking routes have been proposed for membrane proteins: (i) vesicular from ER Golgi then apicoplast, (ii) contiguity between allowing direct flow of proteins, (iii) transport directly Previously, we identified set T. which were also detected large vesicles near organelle....
Toxoplasma gondii, like most apicomplexan parasites, possesses an essential relict chloroplast, the apicoplast. Several apicoplast membrane proteins lack bipartite targeting sequences of luminal proteins. Vesicles bearing these are detected during enlargement, but means cargo selection remains obscure. We used a combination deletion mutagenesis, point mutations and protein chimeras to identify short motif prior first transmembrane domain T. gondii phosphate transporter 1 (APT1) that is...
The malaria parasite Plasmodium falciparum and related organisms possess a relict plastid known as the apicoplast. Apicoplast protein synthesis is validated drug target in because antibiotics that inhibit translation prokaryotes also apicoplast are sometimes used for prophylaxis or treatment. We identified components of an indirect aminoacylation pathway Gln-tRNAGln biosynthesis we hypothesized would be essential synthesis. Here, report our characterization first enzyme this pathway,...