A5003574125- Enzyme Structure and Function
- Melanoma and MAPK Pathways
- Biochemical and Molecular Research
- Microbial Metabolic Engineering and Bioproduction
- Protein Structure and Dynamics
- Cancer Mechanisms and Therapy
- Eosinophilic Esophagitis
- IL-33, ST2, and ILC Pathways
- Computational Drug Discovery Methods
- Advanced Proteomics Techniques and Applications
- Synthesis and biological activity
- Tuberculosis Research and Epidemiology
- Cancer Research and Treatments
- DNA Repair Mechanisms
- Mycobacterium research and diagnosis
- Porphyrin Metabolism and Disorders
- RNA and protein synthesis mechanisms
- Eosinophilic Disorders and Syndromes
- Porphyrin and Phthalocyanine Chemistry
- RNA modifications and cancer
- Cancer therapeutics and mechanisms
- Viral Infectious Diseases and Gene Expression in Insects
- Metabolism and Genetic Disorders
- Heme Oxygenase-1 and Carbon Monoxide
- Colorectal Cancer Treatments and Studies
Cincinnati Children's Hospital Medical Center
2018-2021
University of Cincinnati
2020
Lawrence Berkeley National Laboratory
2010-2012
Scripps Research Institute
2007-2009
University of Georgia
2002-2007
Joint Center for Structural Genomics
2005-2007
University of Toledo
2001-2007
IL-33 is an epithelium-derived, pro-inflammatory alarmin with enigmatic nuclear localization and chromatin binding. Here we report the functional properties of IL-33. Overexpression does not alter global gene expression in transduced epithelial cells. Fluorescence recovery after photobleaching data show that intranuclear mobility ~10-fold slower than IL-1α, whereas truncated lacking chromatin-binding activity more mobile. WT resistant to necrosis-induced release has a relatively slow, linear...
Eosinophilic esophagitis is mediated by uncontrolled proteolytic activity of kallikrein 5 influencing the epithelial barrier and innate immunity.
Given the significant body of data supporting an essential role for c-jun-N-terminal kinase (JNK) in neurodegenerative disorders, we set out to develop highly selective JNK inhibitors with good cell potency and brain penetration properties. The structure−activity relationships (SAR) around a series aminopyrimidines were evaluated utilizing biochemical cell-based assays measure inhibition mice. Microsomal stability three species, P450 inhibition, generation reactive oxygen species (ROS),...
VapBC pairs account for 45 out of 88 identified toxin-antitoxin (TA) in the Mycobacterium tuberculosis (Mtb) H37Rv genome. A working model suggests that under times stress, antitoxin molecules are degraded, releasing toxins to slow metabolism cell, which case VapC is via their RNase activity. Otherwise TA remain bound promoters, autoinhibiting transcription. The crystal structure Rv0301-Rv0300, an Mtb complex determined at 1.49 Å resolution, a mechanism these three functions: activity, its...
Abstract Eosinophilic esophagitis (EoE) is a chronic allergic inflammatory disease with complex underlying genetic etiology. Herein, we conduct whole-exome sequencing of multigeneration EoE pedigree (discovery set) and 61 additional multiplex families (replication set). A series rare, heterozygous, missense variants are identified in the genes encoding desmosome-associated proteins DSP PPL 21% families. Esophageal biopsies from patients these retain dilated intercellular spaces decrease...
Kinases are important drug discovery targets for a wide variety of therapeutic indications; consequently, the measurement kinase activity remains common high-throughput screening (HTS) application.Recently, enzyme-coupled luciferase-kinase (LK) format assays have been introduced.This measures luminescence resulting from metabolism adenosine triphosphate (ATP) via luciferin/luciferase-coupled reaction.In research presented here, 1536-well time-resolved fluorescence resonance energy transfer...
Using a high degree of automation, the crystallography core at Southeast Collaboratory for Structural Genomics (SECSG) has developed high-throughput protein-to-structure pipeline. Various robots and automation procedures have been adopted integrated into pipeline that is capable screening 40 proteins crystallization solving four protein structures per week. This composed three major units: crystallization, structure determination/validation crystallomics. Coupled with protein-production...
The crystal structure of the urease gamma subunit (UreA) from Mycobacterium tuberculosis, Rv1848, has been determined at 1.8 A resolution. asymmetric unit contains three copies Rv1848 arranged into a homotrimer that is similar to UreA trimer in Klebsiella aerogenes. Small-angle X-ray scattering experiments indicate protein also forms trimers solution. observed and organization genes within M. tuberculosis genome suggest (alphabetagamma)(3) composition for other bacterial ureases. may be...
Replication protein A (RPA) is a single-stranded DNA-binding involved in all aspects of eukaryotic DNA metabolism. soluble heterodimeric form RPA composed 14 and 32 kDa subunits (RPA14/32). Dynamic light-scattering (DLS) analysis was used to improve the purification, stabilization crystallization RPA14/32. Increasing concentration reducing agent last stage purification diminished size secondary peak anion-exchange chromatograph promoted single species solution. This resulted decreased...
Mycobacterium tuberculosis (Mtb) is the causative agent of deadly disease tuberculosis. Iron acquisition, regulation and storage are critical for survival this pathogen within a host. Thus, understanding mechanisms iron metabolism in Mtb will shed light on its pathogenic nature, as important infection. Ferritins superfamily protein nanocages that function both detoxification storage, contains predicted ferritin bacterioferritin. Here, cloning, expression, purification, crystallization...
Recently, the demands of high-throughput macromolecular crystallography have driven continuous improvements in phasing methods, data-collection protocols and many other technologies. Single-wavelength anomalous scattering (SAS) with chromium X-ray radiation opens a new possibility for protein data collected in-house has led to several successful examples de novo structure solution using only weak scatterers such as sulfur. To further reduce time make SAS more robust, it is natural combine...
A corrinoid protein was induced and overexpressed in methanol-grown cells of the thermophilic anaerobic bacterium Moorella thermoacetica. The purified from cytosolic extracts. After screening for crystallization conditions optimization, crystals were obtained that diffracted strongly on a rotating-anode X-ray source. diffraction data set collected processed including reflections to 1.9 Å resolution. Reflections indexed primitive orthorhombic cell with unit-cell parameters = 55.69, b 62.74, c...
The gene product of the open reading frame Rv3340 from Mycobacterium tuberculosis is annotated as encoding a probable O-acetylhomoserine (OAH) sulfhydrylase (MetC), an enzyme that catalyzes last step in biosynthesis methionine, which essential amino acid bacteria and plants. Following overexpression Escherichia coli, M. MetC was purified crystallized using hanging-drop vapor-diffusion method. Native diffraction data were collected crystals belonging to space group P21 processed resolution 2.1 Å.
ADVERTISEMENT RETURN TO ISSUEPREVAddition/CorrectionORIGINAL ARTICLEThis notice is a correctionCorrections to Synthesis, Biological Evaluation, X-ray Structure, and Pharmacokinetics of Aminopyrimidine c-jun-N-terminal Kinase (JNK) InhibitorsTed Kamenecka, Rong Jiang, Xinyi Song, Derek Duckett, Weimin Chen, Yuan Ling, Jeff Habel, John D. Laughlin, Jeremy Chambers, Mariana Figuera-Losada, Michael Cameron, Li Lin, Claudia H. Ruiz, Philip V. LoGrasso*Cite this: J. Med. Chem. 2010, 53, 4,...