The formation of dehydroalanine residues in alkali-treated insulin and oxidized glutathione. A nuclear-magnetic-resonance study.
Ontology highlight
ABSTRACT:
SUBMITTER: Jones AJ
PROVIDER: S-EPMC1154384 | biostudies-other | 1983 May
REPOSITORIES: biostudies-other
Similar Datasets
Project description:Chain reversals are often nucleation sites in protein folding. The β-hairpins of FBP28 WW domain and IgG are stable and have been proved to initiate the folding and are, therefore, suitable for studying the influence of charged residues on β-hairpin conformation. In this paper, we carried out NMR examination of the conformations in solution of two fragments from the FPB28 protein (PDB code: 1E0L) (N-terminal part) namely KTADGKT-NH2 (1E0L 12-18, D7) and YKTADGKTY-NH2 (1E0L 11-19, D9), one from the B3 domain of the protein G (PDB code: 1IGD), namely DDATKT-NH2 (1IGD 51-56) (Dag1), and three variants of Dag1 peptide: DVATKT-NH2 (Dag2), OVATKT-NH2 (Dag3) and KVATKT-NH2 (Dag4), respectively, in which the original charged residue were replaced with non-polar residues or modified charged residues. It was found that both the D7 and D9 peptides form a large fraction bent conformations. However, no hydrophobic contacts between the terminal Tyr residues of D9 occur, which suggests that the presence of a pair of like-charged residues stabilizes chain reversal. Conversely, only the Dag1 and Dag2 peptides exhibit some chain reversal; replacing the second aspartic-acid residue with a valine and the first one with a basic residue results in a nearly extended conformation. These results suggest that basic residues farther away in sequence can result in stabilization of chain reversal owing to screening of the non-polar core. Conversely, smaller distance in sequence prohibits this screening, while the presence oppositely-charged residues can stabilize a turn because of salt-bridge formation.
| S-EPMC4239826 | biostudies-literature
Project description:We present a novel method that breaks the resolution barrier in nuclear magnetic resonance (NMR) spectroscopy, allowing one to accurately estimate the chemical shift values of highly overlapping or broadened peaks. This problem is routinely encountered in NMR when peaks have large linewidths due to rapidly decaying signals, hindering its application. We address this problem based on the notion of finite-rate-of-innovation (FRI) sampling, which is based on the premise that signals such as the NMR signal, can be accurately reconstructed using fewer measurements than that required by existing approaches. The FRI approach leads to super-resolution, beyond the limits of contemporary NMR techniques. Using this method, we could measure for the first time small changes in chemical shifts during the formation of a Gold nanorod-protein complex, facilitating the quantification of the strength of such interactions. The method thus opens up new possibilities for the application and acceleration of multidimensional NMR spectroscopy across a wide range of systems.
| S-EPMC5575056 | biostudies-literature
Project description:The exchange of molecules between different physical or chemical environments due to diffusion or chemical transformations has a crucial role in a plethora of fundamental processes such as breathing, protein folding, chemical reactions and catalysis. Here, we introduce a method for a single-scan, ultrafast NMR analysis of molecular exchange based on the diffusion coefficient contrast. The method shortens the experiment time by one to four orders of magnitude. Consequently, it opens the way for high sensitivity quantification of important transient physical and chemical exchange processes such as in cellular metabolism. As a proof of principle, we demonstrate that the method reveals the structure of aggregates formed by surfactants relevant to aerosol research.
| S-EPMC7319991 | biostudies-literature
Project description:Innovative nuclear magnetic resonance approaches have emerged as outstanding means of tracking down functionally important properties of biomolecular assemblies that evade detection. These enigmatic attributes include dynamic equilibria with very lightly populated excited states and structures of complexes obscured by slow tumbling in solution.
| S-EPMC2920670 | biostudies-literature
Project description:?-Thalassemia is a widespread autosomal recessive blood disorder found in most parts of the world. Fetal hemoglobin (HbF), a form of hemoglobin is found in infants, replaced by adult hemoglobin (HbA) after birth. Hydroxyurea (HU) is one of the most effective HbF inducer used for the treatment of anemic diseases. We aimed to improve the understanding of HU therapy in ?-thalassemia by metabonomics approach using 1H NMR spectroscopy. This study includes 40 cases of ?-thalassemia before and after HU therapy along with 40 healthy as controls. Carr-Purcell-Meiboom-Gill (CPMG) sequence was used to identify forty-one putative metabolites. Generation of models like partial least square discriminant analysis (PLS-DA) and orthogonal projections to latent structures discriminant analysis (OPLS-DA) based on different metabolites including lipids, amino acids, glucose, fucose, isobutyrate, and glycerol revealed satisfactory outcomes with 85.2% and 91.1% classification rates, respectively. The concentration of these metabolites was altered in ?-thalassemia samples. However, after HU treatment metabolic profile of same patients showed closeness towards healthy. Deviant metabolic pathways counting lipoprotein changes, glycolysis, TCA cycle, fatty acid and choline metabolisms were identified as having significant differences among study groups. Findings of this study may open a better way to monitor HU treatment effectiveness in ?-thalassemia patients, as the results suggested that metabolic profile of ?-thalassemia patients shows similarity towards normal profile after this therapy.
| S-EPMC6376050 | biostudies-literature
Project description:We have combined ultrasensitive force-based spin detection with high-fidelity spin control to achieve NMR diffraction (NMRd) measurement of ~2 million [Formula: see text]P spins in a [Formula: see text] volume of an indium-phosphide (InP) nanowire. NMRd is a technique originally proposed for studying the structure of periodic arrangements of spins, with complete access to the spectroscopic capabilities of NMR. We describe two experiments that realize NMRd detection with subangstrom precision. In the first experiment, we encode a nanometer-scale spatial modulation of the z-axis magnetization of [Formula: see text]P spins and detect the period and position of the modulation with a precision of <0.8 Å. In the second experiment, we demonstrate an interferometric technique, utilizing NMRd, to detect an angstrom-scale displacement of the InP sample with a precision of 0.07 Å. The diffraction-based techniques developed in this work extend the Fourier-encoding capabilities of NMR to the angstrom scale and demonstrate the potential of NMRd as a tool for probing the structure and dynamics of nanocrystalline materials.
| S-EPMC9546613 | biostudies-literature
Project description:Decrypting the structure, function, and molecular interactions of complex molecular machines in their cellular context and at atomic resolution is of prime importance for understanding fundamental physiological processes. Nuclear magnetic resonance is a well-established imaging method that can visualize cellular entities at the micrometer scale and can be used to obtain 3D atomic structures under in vitro conditions. Here, we introduce a solid-state NMR approach that provides atomic level insights into cell-associated molecular components. By combining dedicated protein production and labeling schemes with tailored solid-state NMR pulse methods, we obtained structural information of a recombinant integral membrane protein and the major endogenous molecular components in a bacterial environment. Our approach permits studying entire cellular compartments as well as cell-associated proteins at the same time and at atomic resolution.
| S-EPMC3323964 | biostudies-literature
Project description:The self-assembly of amyloid proteins into ?-sheet rich assemblies is associated with human amyloidoses including Alzheimer's disease, Parkinson's disease, and type 2 diabetes. An attractive therapeutic strategy therefore is to develop small molecules that would inhibit protein self-assembly. Natural polyphenols are potential inhibitors of ?-sheet formation. How these compounds affect the kinetics of self-assembly studied by thioflavin T (ThT) fluorescence is not understood primarily because their presence interferes with ThT fluorescence. Here, we show that by plotting peak intensities from nuclear magnetic resonance (NMR) against incubation time, kinetic profiles in the presence of the polyphenol can be obtained from which kinetic parameters of self-assembly can be easily determined. In applying this technique to the self-assembly of the islet amyloid polypeptide in the presence of curcumin, a biphenolic compound found in turmeric, we show that the kinetic profile is atypical in that it shows a prenucleation period during which there is no observable decrease in NMR peak intensities.
| S-EPMC4025671 | biostudies-literature
Project description:Palladium/neocuproine catalyzed oxidation of glucosides shows an excellent selectivity for the C3-OH, but in mannosides and galactosides, unselective oxidation was initially observed. For further application in more-complex (oligo)saccharides, a better understanding of the reaction, in terms of selectivity and reactivity, is required. Therefore, a panel of different glycosides was synthesized, subjected to palladium/neocuproine catalyzed oxidation and subsequently analyzed by qNMR. Surprisingly, all studied glucosides, mannosides, galactosides, and xylosides show selective oxidation of the C3-OH. However, subsequent reaction of the resulting ketone moiety is the main culprit for side product formation. Measures are reported to suppress these side reactions. The observed differences in reaction rate, glucosides being the most rapidly oxidized, may be exploited for the selective oxidation of complex oligosaccharides.
| S-EPMC5370080 | biostudies-literature
Project description:BACKGROUND: Drug discovery is a complex and unpredictable endeavor with a high failure rate. Current trends in the pharmaceutical industry have exasperated these challenges and are contributing to the dramatic decline in productivity observed over the last decade. The industrialization of science by forcing the drug discovery process to adhere to assembly-line protocols is imposing unnecessary restrictions, such as short project time-lines. Recent advances in nuclear magnetic resonance are responding to these self-imposed limitations and are providing opportunities to increase the success rate of drug discovery. OBJECTIVE/METHOD: A review of recent advancements in NMR technology that have the potential of significantly impacting and benefiting the drug discovery process will be presented. These include fast NMR data collection protocols and high-throughput protein structure determination, rapid protein-ligand co-structure determination, lead discovery using fragment-based NMR affinity screens, NMR metabolomics to monitor in vivo efficacy and toxicity for lead compounds, and the identification of new therapeutic targets through the functional annotation of proteins by FAST-NMR. CONCLUSION: NMR is a critical component of the drug discovery process, where the versatility of the technique enables it to continually expand and evolve its role. NMR is expected to maintain this growth over the next decade with advancements in automation, speed of structure calculation, in-cell imaging techniques, and the expansion of NMR amenable targets.
| S-EPMC2843924 | biostudies-literature