Track topics on Twitter Track topics that are important to you
The inactive state of mitogen activated protein kinases (MAPKs) adopts an open conformation while the active state exists in a compact form stabilized by phosphorylation. In the active state, eukaryotic kinases undergo breathing motions related to substrate binding and product release that have not previously been detected in the inactive state. However, docking interactions of partner proteins with inactive MAPK kinases exhibit allostery in binding of activating kinases: interactions at a site distant from the activation loop are coupled to the configuration of the activation loop, suggesting that the inactive state may also undergo concerted dynamics. X-ray crystallographic studies of non-phosphorylated, inactive p38γ reveal differences in domain orientations and active site structure in the two molecules in the asymmetric unit. One molecule resembles an inactive kinase, with an open active site. The second molecule has a rotation of the N-lobe that leads to partial compaction of the active site, resulting in a conformation that is intermediate between the inactive open state and the fully closed state of the activated kinase. Although the compact state of apo p38γ displays several of the features of the activated enzyme, it remains catalytically inert. In solution, the kinase fluctuates on a millisecond timescale between the open ground state and a weakly populated excited state that is similar in structure to the compact state observed in the crystal. The NMR and crystal structure data imply that interconversion between the open and compact states involves a molecular switch associated with the DFG loop.
This article was published in the following journal.
We report quantum chemical calculations using multireference perturbation theory (MRPT) with the density matrix renormalization group (DMRG) plus photothermal deflection spectroscopy measurements to i...
The influence of torsional disorder around the ethynyl π-bridges of a linear D-π-A-π-D molecule on the nature of its S excited state was investigated using ultrafast time-resolved infrared spectros...
Excited states of tris(2,2'-bipyridine)ruthenium(II), [Ru(bpy)], can be deactivated by a wide range of ferrocene derivatives. The pathway by which deactivation takes place, either energy transfer (EnT...
We present a method for finding individual excited states' energy stationary points in complete active space self-consistent field theory that is compatible with standard optimization methods and high...
The widely expressed G-protein coupled receptors (GPCRs) are versatile signal transducer proteins that are attractive drug targets but structurally challenging to study. GPCRs undergo a number of conf...
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...
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...
The goal of this study compare the effectiveness of an electronic note versus a telephone call to alert the prescriber of a possible IV to oral switch. Secondary endpoints are the time-to-...
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...
Introduction: Sleep disturbances may contribute to impairments in mood, occupational and intellectual performance, and social relationships, as well as being associated with cardiovascular...
Genes that cause the epigenotype (i.e., the interrelated developmental pathways through which the adult organism is realized) to switch to an alternate cell lineage-related pathway. Switch complexes control the expression of normal functional development as well as oncogenic transformation.
Emission of LIGHT when ELECTRONS return to the electronic ground state from an excited state and lose the energy as PHOTONS. It is sometimes called cool light in contrast to INCANDESCENCE. LUMINESCENT MEASUREMENTS take advantage of this type of light emitted from LUMINESCENT AGENTS.
Physiologically inactive substances that can be converted to active enzymes.
The first committed enzyme of the biosynthesis pathway that leads to the production of STEROLS. it catalyzes the synthesis of SQUALENE from farnesyl pyrophosphate via the intermediate PRESQUALENE PYROPHOSPHATE. This enzyme is also a critical branch point enzyme in the biosynthesis of ISOPRENOIDS that is thought to regulate the flux of isoprene intermediates through the sterol pathway.
A site located in the INTRONS at the 5' end of each constant region segment of a immunoglobulin heavy-chain gene where recombination (or rearrangement) occur during IMMUNOGLOBULIN CLASS SWITCHING. Ig switch regions are found on genes encoding all five classes (IMMUNOGLOBULIN ISOTYPES) of IMMUNOGLOBULIN HEAVY CHAINS.
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...
Collaborations in biotechnology
Commercial and academic collaborations are used throughout the biotechnology and pharmaceutical sector to enhance research and product development. Collaborations can take the form of research and evaluation agreements, licensing, partnerships etc. ...