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PKR is a member of the eIF2α family of protein kinases that inhibit translational initiation in response to stress stimuli and functions as a key mediator of the interferon-induced antiviral response. PKR contains a dsRNA binding domain that bind to duplex regions present in viral RNAs, resulting in kinase activation and autophosphorylation. An emerging theme in the regulation of protein kinases is the allosteric linkage of dimerization and activation. The PKR kinase domain forms a back-to-back parallel dimer which is implicated in activation. We have developed a sensitive homo-FRET assay for kinase domain dimerization to directly probe the relationship between RNA binding, activation, and dimerization. In the case of perfect duplex RNAs, dimerization is correlated with activation and dsRNAs containing 30 bp or more efficiently induce kinase domain dimerization and activation. However, more complex duplex RNAs containing a 10-15 bp 2'-O-methyl RNA barrier produce kinase dimers but do not activate. Similarly, inactivating mutations within the PKR dimer interface that disrupt key electrostatic and hydrogen binding interactions fail to abolish dimerization. Our data support a model where activating RNAs induce formation of a back-to-back parallel PKR kinase dimer whereas nonactivating RNAs either fail to induce dimerization or produce an alternative, inactive dimer configuration, providing an additional mechanism for distinguishing between host and pathogen RNA.
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IS-family transposons are unusual because they do not have terminal inverted repeats or generate target site duplications. They encode two protein-coding genes, but only is required for transposition...
Dimers of furan, 2,3-dihydrofuran, 2,5-dihydrofuran and tetrahydrofuran were investigated with the use of theoretical methods to determine the interactions that keep the molecules together. The QTAIM ...
Recurrent aphthous stomatitis (RAS) is associated with endothelial dysfunction and chronic inflammation. The neutrophil-to-lymphocyte ratio (NLR) and mean platelet voume (MPV) are markers of inflammat...
Many protein kinases are characterized by at least two structural forms corresponding to the highest level of activity (active) and low or no activity, (inactive). Further, protein dynamics is an impo...
Quinoline and quinolone motifs which act as structural subunits of more complex natural products are ubiquitous in nature, and they are useful pharmacophores which play a pivotal role in drug developm...
The purpose of this study is to investigate the natural kinetics of D-dimers that occur after abdominal surgery.
The purpose of this study is to understand what happens when someone either becomes more active or more inactive. This study will measure your energy intake, energy expenditure, and body c...
Patients with atrial fibrillation are at increased risk of thrombus formation in the left heart, especially in the auricula and the atrium. Their presence increases the risk of ischemic st...
Currently, the traditional disease activity of Takayasu arteritis is mainly based on National Institutes of Health criteria and the inactive cases don't need anti-inflammatory treatment. H...
Recent evidence suggests that patients with inactive chronic hepatitis B (CHB) may develop the same types of liver complications that patients in the active state of hepatitis B virus (HBV...
Dimers found in DNA chains damaged by ULTRAVIOLET RAYS. They consist of two adjacent PYRIMIDINE NUCLEOTIDES, usually THYMINE nucleotides, in which the pyrimidine residues are covalently joined by a cyclobutane ring. These dimers block DNA REPLICATION.
Physiologically inactive substances that can be converted to active enzymes.
A group of indole-indoline dimers which are ALKALOIDS obtained from the VINCA genus of plants. They inhibit polymerization of TUBULIN into MICROTUBULES thus blocking spindle formation and arresting cells in METAPHASE. They are some of the most useful ANTINEOPLASTIC AGENTS.
An enzyme that catalyzes the conversion of phosphorylated, inactive glycogen synthase D to active dephosphoglycogen synthase I. EC 126.96.36.199.
A naturally occurring glucocorticoid. It has been used in replacement therapy for adrenal insufficiency and as an anti-inflammatory agent. Cortisone itself is inactive. It is converted in the liver to the active metabolite HYDROCORTISONE. (From Martindale, The Extra Pharmacopoeia, 30th ed, p726)
Within medicine, nutrition (the study of food and the effect of its components on the body) has many different roles. Appropriate nutrition can help prevent certain diseases, or treat others. In critically ill patients, artificial feeding by tubes need t...