Search results for "Conformational change"
showing 10 items of 69 documents
Effect of T-R conformational change on sickle-cell hemoglobin interactions and aggregation
2004
We compare the role of a conformational switch and that of a point mutation in the thermodynamic stability of a protein solution and in the consequent propensity toward aggregation. We study sickle-cell hemoglobin (HbS), the beta6 Glu-Val point mutant of adult human hemoglobin (HbA), in its R (CO-liganded) conformation, and compare its aggregation properties to those of both HbS and HbA in their T (unliganded) conformation. Static and dynamic light scattering measurements performed for various hemoglobin concentrations showed critical divergences with mean field exponents as temperature was increased. This allowed determining spinodal data points T(S)(c) by extrapolation. These points were …
Multiscale Simulations of SARS-CoV-2 3CL Protease Inhibition with Aldehyde Derivatives. Role of Protein and Inhibitor Conformational Changes in the R…
2021
We here investigate the mechanism of SARS-CoV-2 3CL protease inhibition by one of the most promising families of inhibitors, those containing an aldehyde group as a warhead. These compounds are covalent inhibitors that inactivate the protease, forming a stable hemithioacetal complex. Inhibitor 11a is a potent inhibitor that has been already tested in vitro and in animals. Using a combination of classical and QM/MM simulations, we determined the binding mode of the inhibitor into the active site and the preferred rotameric state of the catalytic histidine. In the noncovalent complex, the aldehyde group is accommodated into the oxyanion hole formed by the NH main-chain groups of residues 143 …
Adsorption and Conformation Behavior of Biotinylated Fibronectin on Streptavidin-Modified TiOX Surfaces Studied by SPR and AFM
2011
It is well-known that protein-modified implant surfaces such as TiO(2) show a higher bioconductivity. Fibronectin is a glycoprotein from the extracellular matrix (ECM) with a major role in cell adhesion. It can be applied on titanium oxide surfaces to accelerate implant integration. Not only the surface concentration but also the presentation of the protein plays an important role for the cellular response. We were able to show that TiO(X) surfaces modified with biotinylated fibronectin adsorbed on a streptavidin-silane self-assembly multilayer system are more effective regarding osteoblast adhesion than surfaces modified with nonspecifically bound fibronectin. The adsorption and conformati…
1H NMR and UV-vis spectroscopic characterization of sulfonamide complexes of nickek(II)-carbonic anhydrase. Resonance assignments based on NOE effects
1992
The binding of acetazolamide, p-fluorobenzensulfonamide, p-toluenesulfonamide, and sulfanilamide to nickel(II)-substituted carbonic anhydrase II has been studied by 1H NMR and electronic absorption spectroscopies. These inhibitors bind to the metal ion forming 1:1 complexes and their affinity constants were determined. The 1H NMR spectra of the formed complexes show a number of isotropically shifted signals corresponding to the histidine ligands. The complexes with benzene-sulfonamides gave rise to very similar 1H NMR spectra. The NMR data suggest that these aromatic sulfonamides bind to the metal ion altering its coordination sphere. In addition, from the temperature dependence of 1H NMR s…
Interactions between aroma compounds and beta-lactoglobulin in the heat-induced molten globule state
2010
; he present study aims to elucidate the binding of small hydrophobic ligands onto the molten globule state of β-lactoglobulin (BLG). The conversion of the native BLG into a molten globule state was induced by heat treatment at acidic pH. The molten globule state was evidenced by far and near-UV circular dichroism spectra. β-Ionone and guaiacol exhibited a higher binding ability to BLG in the heat-induced molten globule state compared to unheated BLG, as assessed by protein surface hydrophobicity measurements, using 6-propionyl-2-(dimethylamino)naphthalene (PRODAN) fluorescent probe. The binding sites of the two aroma compounds were determined by 2D nuclear magnetic resonance (NMR) spectro…
Thermal aggregation of proteins in presence of metal ions.
2008
The study of the aggregation processes in presence of metal ions is an essential step for understanding the key role of metals in protein-protein and protein-solvent interactions. Indeed, the presence of metal ions can radically change the main features of the standard denaturation/aggregation processes and such effects result to be strongly dependent on the kind of metal and on its concentration. Metal ions have an active role in thermal aggregation and cold set gelation processes. These processes are intrinsically different, but both are based on the proteins ability to form aggregates.
Structure and function of ferredoxin-NADP+-oxidoreductase
1987
The redox-enzyme ferredoxin-NADP-oxidoreductase has been shown to be activated by light and inactivated in the dark. This review will summarize recent data concerning the biochemical characterization of the enzyme compared to its in-vivo activation. Further-more the mechanism of this activation process is discussed as a conformational change caused by the light-driven proton gradient.
Weak non-covalent interactions control the relative molecular orientation in the crystals of N-pentafluorobenzyl aniline derivatives
2010
The crystal structures of N-pentafluorobenzyl aniline derivatives are controlled by versatile aromatic–aromatic interactions between the electron deficient and electron rich aromatics; the parent compound (1) possesses an L shape while protonation (2–5) induces a conformational change resulting in a planar arrangement of molecules which pack in layer type structures with different molecular orientations.
Bile acid–amino acid ester conjugates: gelation, structural properties, and thermoreversible solid to solid phase transition
2010
Design, synthesis, and gelation properties of three novel biocompatible bile acid–L-methionine methyl ester conjugates are presented. Two of the conjugates have been shown to undergo self-assembly leading to organogelation in certain aromatic solvents. The properties of these gels have been investigated by conventional methods typical for molecular gel studies along with 13C CPMAS NMR spectroscopic studies of the native gel. In addition, properties in solid and solution states for all three compounds have been investigated, and single crystal X-ray structures of all compounds determined. Furthermore, powder X-ray diffraction studies have revealed that compound 1 undergoes a dynamic and reve…
Cooperative symmetric to asymmetric conformational transition of the apo-form of scavenger decapping enzyme revealed by simulations.
2007
Decapping is a central step in eukaryotic mRNA turnover and in gene expression regulation. The human scavenger decapping enzyme, DcpS, catalyses cap hydrolysis following mRNA degradation. DcpS is a dimeric enzyme, with two active sites. Crystal structures suggest that DcpS must undergo significant conformational changes upon ligand binding, but the mechanism of this transition is unknown. Here, we report two long timescale (20 ns) molecular dynamics simulations of the apo-form of DcpS. The dimer is observed to undergo a strikingly cooperative motion, with one active site closing while the other opens. The amplitude of the conformational change is 6–21 A and the apparent timescale is 4–13 ns…