Search results for "Interactions"
showing 10 items of 1963 documents
The Protein Structure Context of PolyQ Regions.
2016
Proteins containing glutamine repeats (polyQ) are known to be structurally unstable. Abnormal expansion of polyQ in some proteins exceeding a certain threshold leads to neurodegenerative disease, a symptom of which are protein aggregates. This has led to extensive research of the structure of polyQ stretches. However, the accumulation of contradictory results suggests that protein context might be of importance. Here we aimed to evaluate the structural context of polyQ regions in proteins by analysing the secondary structure of polyQ proteins and their homologs. The results revealed that the secondary structure in polyQ vicinity is predominantly random coil or helix. Importantly, the region…
Mass Spectrometry and Structural Biology Techniques in the Studies on the Coronavirus-Receptor Interaction
2020
Mass spectrometry and some other biophysical methods, have made substantial contributions to the studies on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and human proteins interactions. The most interesting feature of SARS-CoV-2 seems to be the structure of its spike (S) protein and its interaction with the human cell receptor. Mass spectrometry of spike S protein revealed how the glycoforms are distributed across the S protein surface. X-ray crystallography and cryo-electron microscopy made huge impact on the studies on the S protein and ACE2 receptor protein interaction, by elucidating the three-dimensional structures of these proteins and their conformational changes. The…
Design, synthesis, and biological evaluation of novel disubstituted dibenzosuberones as highly potent and selective inhibitors of p38 mitogen activat…
2012
Synthesis, biological testing, structure-activity relationships (SARs), and selectivity of novel disubstituted dibenzosuberone derivatives as p38 MAP kinase inhibitors are described. Hydrophilic moieties were introduced at the 7-, 8-, and 9-position of the 2-phenylamino-dibenzosuberones, improving physicochemical properties as well as potency. Extremely potent inhibitors were obtained, with half-maximal inhibitory concentration (IC(50)) values in the low nM range in a whole blood assay measuring the inhibition of cytokine release. The high potency of the target compounds together with the outstanding selectivity of this novel class of compounds toward p38 mitogen activated protein (MAP) kin…
Genomic determinants of protein folding thermodynamics in prokaryotic organisms.
2004
Here we investigate how thermodynamic properties of orthologous proteins are influenced by the genomic environment in which they evolve. We performed a comparative computational study of 21 protein families in 73 prokaryotic species and obtained the following main results. (i) Protein stability with respect to the unfolded state and with respect to misfolding are anticorrelated. There appears to be a trade-off between these two properties, which cannot be optimized simultaneously. (ii) Folding thermodynamic parameters are strongly correlated with two genomic features, genome size and G+C composition. In particular, the normalized energy gap, an indicator of folding efficiency in statistical…
Evidence for Water-Tuned Structural Differences in Proteins: An Approach Emphasizing Variations in Local Hydrophilicity
2012
We present experimental evidence for the significant effect that water can have on the functional structure of proteins in solution. Human (HSA) and Bovine Serum Albumin (BSA) have an amino acid sequence identity of 75.52% and are chosen as model proteins. We employ EPR-based nanoscale distance measurements using double electron-electron resonance (DEER) spectroscopy and both albumins loaded with long chain fatty acids (FAs) in solution to globally (yet indirectly) characterize the tertiary protein structures from the bound ligands' points of view. The complete primary structures and crystal structures of HSA and as of recently also BSA are available. We complement the picture as we have re…
Proteome response of Tribolium castaneum larvae to Bacillus thuringiensis toxin producing strains.
2012
Susceptibility of Tribolium castaneum (Tc) larvae was determined against spore-crystal mixtures of five coleopteran specific and one lepidopteran specific Bacillus thuringiensis Cry toxin producing strains and those containing the structurally unrelated Cry3Ba and Cry23Aa/Cry37Aa proteins were found toxic (LC(50) values 13.53 and 6.30 µg spore-crystal mixture/µL flour disc, respectively). Using iTRAQ combined with LC-MS/MS allowed the discovery of seven novel differentially expressed proteins in early response of Tc larvae to the two active spore-crystal mixtures. Proteins showing a statistically significant change in treated larvae compared to non-intoxicated larvae fell into two major cat…
Topology and accessibility of the transmembrane helices and the sensory site in the bifunctional transporter DcuB of Escherichia coli.
2011
C(4)-Dicarboxylate uptake transporter B (DcuB) of Escherichia coli is a bifunctional transporter that catalyzes fumarate/succinate antiport and serves as a cosensor of the sensor kinase DcuS. Sites and domains of DcuB were analyzed for their topology relative to the cytoplasmic or periplasmic side of the membrane and their accessibility to the water space. For the topology studies, DcuB was fused at 33 sites to the reporter enzymes PhoA and LacZ that are only active when located in the periplasm or the cytoplasm, respectively. The ratios of the PhoA and LacZ activities suggested the presence of 10 or 11 hydrophilic loops, and 11 or 12 α-helical transmembrane domains (TMDs). The central part…
Small-angle X-ray scattering reveals compact domain-domain interactions in the N-terminal region of filamin C
2014
Filamins are multi-domain, actin cross-linking, and scaffolding proteins. In addition to the actin cross-linking function, filamins have a role in mechanosensor signaling. The mechanosensor function is mediated by domain-domain interaction in the C-terminal region of filamins. Recently, we have shown that there is a three-domain interaction module in the Nterminal region of filamins, where the neighboring domains stabilize the structure of the middle domain and thereby regulate its interaction with ligands. In this study, we have used small-angle X-ray scattering as a tool to screen for potential domain-domain interactions in the N-terminal region. We found evidence of four domain-domain in…
A thermodynamic insight into the recognition of hydrophilic and hydrophobic amino acids in pure water by aza-scorpiand type receptors.
2014
Interactions of different hydrophilic (His, Asp, Glu,) and hydrophobic (Ala, Phe, Tyr, Trp) amino acids in water with a scorpiand aza-macrocycle (L1) containing a pyridine group in the ring and its derivative (L2) bearing a naphthalene group in the tail have been analysed by potentiometric and calorimetric measurements. Theoretical calculations corroborate that major attractive forces that hold the adduct together are hydrogen bonds and salt-bridges, even though other interactions such as π-stacking or NH(+)⋯π may contribute in the case of hydrophobic amino acids and L2. Calorimetric measurements indicate that the interactions between L1 and the different amino acids are principally driven …
Modeling of the role of conformational dynamics in kinetics of the antigen-antibody interaction in heterogeneous phase.
2012
[EN] A novel approach that may potentially be used to study biomolecular interactions including the simultaneous determination of structural and kinetic binding parameters is described in this Article for the first time. It allows a rigid distinction between the possible reaction mechanisms of biomolecular recognition, induced fit and conformational selection. The relative importance of the two pathways is determined not by comparing rate constants but the structural aspects of the interaction instead. So the exact location of antigen molecules with respect to the capture antibody is depicted experimentally, avoiding the use of X-ray crystallography. The proposed pattern is applied to study…