[NMR paper] pH Effects Can Dominate Chemical Shift Perturbations in 1H,15N-HSQC NMR Spectroscopy for Studies of Small Molecule/?-Synuclein Interactions
¹H,^(15)N-Heteronuclear Single Quantum Coherence (HSQC) NMR is a powerful technique that has been employed to characterize small-molecule interactions with intrinsically disordered monomeric ?-Synuclein (aSyn). We report how solution pH can impact the interpretation of aSyn HSQC NMR spectra and demonstrate that small-molecule formulations (e.g., complexation with acidic salts) can lower sample pH and confound interpretation of drug binding and concomitant protein structural changes. Through...
Solid-state NMR chemical-shift perturbations indicate domain reorientation of the DnaG primase in the primosome of Helicobacter pylori
Solid-state NMR chemical-shift perturbations indicate domain reorientation of the DnaG primase in the primosome of Helicobacter pylori
Abstract
We here investigate the interactions between the DnaB helicase and the C-terminal domain of the corresponding DnaG primase of Helicobacter pylori using solid-state NMR. The difficult crystallization of this 387Â*kDa complex, where the two proteins interact in a six to three ratio, is circumvented by simple co-sedimentation of the two proteins directly into the MAS-NMR rotor. While the amount of information...
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03-10-2016 10:40 PM
Proteinâ??ligand structure guided by backbone and side-chain proton chemical shift perturbations
Proteinâ??ligand structure guided by backbone and side-chain proton chemical shift perturbations
Abstract
The fragment-based drug design approach consists of screening libraries of fragment-like ligands, to identify hits that typically bind the protein target with weak affinity ( \(100\,\upmu \hbox {M}\) â??5Â*mM). The determination of the proteinâ??fragment complex 3D structure constitutes a crucial step for uncovering the key interactions responsible for...
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09-26-2014 01:03 PM
Antidiabetic effects of glucokinase regulatory protein small-molecule disruptors - Nature.com
Antidiabetic effects of glucokinase regulatory protein small-molecule disruptors - Nature.com
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Antidiabetic effects of glucokinase regulatory protein small-molecule disruptors
Nature.com
In hepatocytes, GK regulates glucose uptake and glycogen synthesis, suppresses glucose production3, 5, and is subject to the endogenous inhibitor GK regulatory protein (GKRP)6, 7, 8. During fasting, GKRP binds, inactivates and ..... 1H-, 13C- and 19F ...
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11-16-2013 03:09 AM
[NMR paper] Protein Dielectric Constants Determined from NMR Chemical Shift Perturbations.
Protein Dielectric Constants Determined from NMR Chemical Shift Perturbations.
Protein Dielectric Constants Determined from NMR Chemical Shift Perturbations.
J Am Chem Soc. 2013 Oct 14;
Authors: Kukic P, Farrell D, McIntosh LP, Garcia-Moreno E B, Jensen KS, Toleikis Z, Teilum K, Nielsen JE
Abstract
Understanding the connection between protein structure and function requires a quantitative understanding of electrostatic effects. Structure-based electrostatics calculations are essential for this purpose, but their use have been limited by a...
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10-16-2013 11:22 AM
[NMR paper] Screening protein-small molecule interactions by NMR.
Screening protein-small molecule interactions by NMR.
Related Articles Screening protein-small molecule interactions by NMR.
Methods Mol Biol. 2013;1008:389-413
Authors: Davis B
Abstract
Nuclear magnetic resonance (NMR) is well suited to probing the interactions between ligands and macromolecular receptors. It is a truly label-free technique, requiring only the presence of atoms (usually (1)H or (19)F) which give rise to observable resonances on either the ligand or the receptor. A number of parameters associated with these resonances can...
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06-05-2013 06:53 PM
Understanding small-molecule binding to MDM2: insights into structural effects of isoindolinone inhibitors from NMR spectroscopy.
Understanding small-molecule binding to MDM2: insights into structural effects of isoindolinone inhibitors from NMR spectroscopy.
Understanding small-molecule binding to MDM2: insights into structural effects of isoindolinone inhibitors from NMR spectroscopy.
Chem Biol Drug Des. 2011 May;77(5):301-8
Authors: Riedinger C, Noble ME, Wright DJ, Mulks F, Hardcastle IR, Endicott JA, McDonnell JM
The interaction between murine double minute (MDM2) and p53 is a major target in anticancer drug design. Several potent compound series, including the nutlins...
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08-05-2011 11:48 AM
31P NMR correlation maps of 18O/16O chemical shift isotopic effects for phosphometabolite labeling studies
31P NMR correlation maps of 18O/16O chemical shift isotopic effects for phosphometabolite labeling studies
Abstract Intramolecular correlations among the 18O-labels of metabolic oligophosphates, mapped by J-decoupled 31P NMR 2D chemical shift correlation spectroscopy, impart stringent constraints to the 18O-isotope distributions over the whole oligophosphate moiety. The multiple deduced correlations of isotopic labels enable determination of site-specific fractional isotope enrichments and unravel the isotopologue statistics. This approach ensures accurate determination of 18O-labeling...
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06-06-2011 12:53 AM
Two-dimensional concurrent HMQC-COSY as an approach for small molecule chemical shift assignment and compound identification
Two-dimensional concurrent HMQC-COSY as an approach for small molecule chemical shift assignment and compound identification
Abstract Chemical shift assignment is the first step toward the structure elucidation of natural products and other chemical compounds. We propose here the use of 2D concurrent HMQC-COSY as an experiment for rapid chemical shift assignment of small molecules. This experiment provides well-dispersed 1Hâ??13C peak patterns that are distinctive for different functional groups plus 1Hâ??1H COSY connectivities that serve to identify adjacent groups. The COSY diagonal...
pH Effects Can Dominate Chemical Shift Perturbations in 1H,15N-HSQC NMR Spectroscopy for Studies of Small Molecule/?-Synuclein Interactions
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