Kinetic andJ-Resolved Statistical Total Correlation NMR Spectroscopy Approaches to Structural Information Recovery in Complex Reacting Mixtures: Application to Acyl Glucuronide Intramolecular Transacylation Reactions

2008 ◽  
Vol 80 (13) ◽  
pp. 4886-4895 ◽  
Author(s):  
Caroline H. Johnson ◽  
Toby J. Athersuch ◽  
Ian D. Wilson ◽  
Lisa Iddon ◽  
Xiaoli Meng ◽  
...  
Keyword(s):  
Nmr Spectroscopy ◽  
Structural Information ◽  
Information Recovery ◽  
Acyl Glucuronide ◽  
Total Correlation ◽  
Reacting Mixtures

scholarly journals The Application of NMR Spectroscopy and Chemometrics in Authentication of Spices

Molecules ◽  
2021 ◽  
Vol 26 (2) ◽  
pp. 382
Author(s):  
Barbara Pacholczyk-Sienicka ◽  
Grzegorz Ciepielowski ◽  
Łukasz Albrecht
Keyword(s):  
Quality Assurance ◽  
Nmr Spectroscopy ◽  
Sample Preparation ◽  
Bioactive Compounds ◽  
Analytical Methods ◽  
Structural Information ◽  
Chemometric Analysis ◽  
Spectroscopic Methods ◽  
Regular Consumption ◽  
No Sample Preparation

Spices and herbs are among the most commonly adulterated food types. This is because spices are widely used to process food. Spices not only enhance the flavor and taste of food, but they are also sources of numerous bioactive compounds that are significantly beneficial for health. The healing effects of spices are connected with their antimicrobial, anti-inflammatory and carminative properties. However, regular consumption of adulterated spices may cause fatal damage to our system because adulterants in most cases are unhealthy. For that reason, the appropriate analytical methods are necessary for quality assurance and to ensure the authenticity of spices. Spectroscopic methods are gaining interest as they are fast, require little or no sample preparation, and provide rich structural information. This review provides an overview of the application of NMR spectroscopy combined with chemometric analysis to determine the quality and adulteration of spices.

Investigation of the structure of regulatory proteins interacting with glycosaminoglycans by combining NMR spectroscopy and molecular modeling – the beginning of a wonderful friendship

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Georg Künze ◽  
Daniel Huster ◽  
Sergey A. Samsonov
Keyword(s):  
Nmr Spectroscopy ◽  
Structural Information ◽  
Md Simulations ◽  
Specific Protein ◽  
Regulatory Proteins ◽  
Structural Constraints ◽  
Modeling Tools ◽  
Nuclear Overhauser ◽  
Nmr Methods ◽  
High Flexibility

Abstract The interaction of regulatory proteins with extracellular matrix or cell surface-anchored glycosaminoglycans (GAGs) plays important roles in molecular recognition, wound healing, growth, inflammation and many other processes. In spite of their high biological relevance, protein-GAG complexes are significantly underrepresented in structural databases because standard tools for structure determination experience difficulties in studying these complexes. Co-crystallization with subsequent X-ray analysis is hampered by the high flexibility of GAGs. NMR spectroscopy experiences difficulties related to the periodic nature of the GAGs and the sparse proton network between protein and GAG with distances that typically exceed the detection limit of nuclear Overhauser enhancement spectroscopy. In contrast, computer modeling tools have advanced over the last years delivering specific protein-GAG docking approaches successfully complemented with molecular dynamics (MD)-based analysis. Especially the combination of NMR spectroscopy in solution providing sparse structural constraints with molecular docking and MD simulations represents a useful synergy of forces to describe the structure of protein-GAG complexes. Here we review recent methodological progress in this field and bring up examples where the combination of new NMR methods along with cutting-edge modeling has yielded detailed structural information on complexes of highly relevant cytokines with GAGs.

Protein structure by solid-state NMR spectroscopy

1987 ◽  
Vol 19 (1-2) ◽  
pp. 7-49 ◽  
Author(s):  
S. J. Opella ◽  
P. L. Stewart ◽  
K. G. Valentine
Keyword(s):  
Solid State ◽  
Nmr Spectroscopy ◽  
Solid State Nmr ◽  
Structural Information ◽  
Biological Systems ◽  
Genetic Regulation ◽  
Protein Structures ◽  
Crystalline Solid ◽  
Solid State Nmr Spectroscopy ◽  
Nmr Methods

The three-dimensional structures of proteins are among the most valuable contributions of biophysics to the understanding of biological systems (Dickerson & Geis, 1969; Creighton, 1983). Protein structures are utilized in the description and interpretation of a wide variety of biological phenomena, including genetic regulation, enzyme mechanisms, antibody recognition, cellular energetics, and macroscopic mechanical and structural properties of molecular assemblies. Virtually all of the information currently available about the structures of proteins at atomic resolution has been obtained from diffraction studies of single crystals of proteins (Wyckoff et al, 1985). However, recently developed NMR methods are capable of determining the structures of proteins and are now being applied to a variety of systems, including proteins in solution and other non-crystalline environments that are not amenable for X-ray diffraction studies. Solid-state NMR methods are useful for proteins that undergo limited overall reorientation by virtue of their being in the crystalline solid state or integral parts of supramolecular structures that do not reorient rapidly in solution. For reviews of applications of solid-state NMR spectroscopy to biological systems see Torchia and VanderHart (1979), Griffin (1981), Oldfield et al. (1982), Opella (1982), Torchia (1982), Gauesh (1984), Torchia (1984) and Opella (1986). This review describes how solid-state NMR can be used to obtain structural information about proteins. Methods applicable to samples with macroscopic orientation are emphasized.

scholarly journals How internal cavities destabilize a protein

2019 ◽  
Vol 116 (42) ◽  
pp. 21031-21036 ◽  
Author(s):  
Mengjun Xue ◽  
Takuro Wakamoto ◽  
Camilla Kejlberg ◽  
Yuichi Yoshimura ◽  
Tania Aaquist Nielsen ◽  
...  
Keyword(s):  
Nmr Spectroscopy ◽  
Molar Volume ◽  
Excited States ◽  
Partial Molar Volume ◽  
Protein Misfolding ◽  
Structural Information ◽  
Relaxation Dispersion ◽  
Internal Cavity ◽  
Cavity Volume ◽  
Internal Cavities

Although many proteins possess a distinct folded structure lying at a minimum in a funneled free energy landscape, thermal energy causes any protein to continuously access lowly populated excited states. The existence of excited states is an integral part of biological function. Although transitions into the excited states may lead to protein misfolding and aggregation, little structural information is currently available for them. Here, we show how NMR spectroscopy, coupled with pressure perturbation, brings these elusive species to light. As pressure acts to favor states with lower partial molar volume, NMR follows the ensuing change in the equilibrium spectroscopically, with residue-specific resolution. For T4 lysozyme L99A, relaxation dispersion NMR was used to follow the increase in population of a previously identified “invisible” folded state with pressure, as this is driven by the reduction in cavity volume by the flipping-in of a surface aromatic group. Furthermore, multiple partly disordered excited states were detected at equilibrium using pressure-dependent H/D exchange NMR spectroscopy. Here, unfolding reduced partial molar volume by the removal of empty internal cavities and packing imperfections through subglobal and global unfolding. A close correspondence was found for the distinct pressure sensitivities of various parts of the protein and the amount of internal cavity volume that was lost in each unfolding event. The free energies and populations of excited states allowed us to determine the energetic penalty of empty internal protein cavities to be 36 cal⋅Å−3.

Statistical Total Correlation Spectroscopy Editing of1H NMR Spectra of Biofluids: Application to Drug Metabolite Profile Identification and Enhanced Information Recovery

2009 ◽  
Vol 81 (15) ◽  
pp. 6458-6466 ◽  
Author(s):  
Caroline J. Sands ◽  
Muireann Coen ◽  
Anthony D. Maher ◽  
Timothy M. D. Ebbels ◽  
Elaine Holmes ◽  
...  
Keyword(s):  
Nmr Spectra ◽  
Metabolite Profile ◽  
Correlation Spectroscopy ◽  
Information Recovery ◽  
Total Correlation ◽  
Drug Metabolite

scholarly journals Insights into Structures and Dynamics of Flavivirus Proteases from NMR Studies

2020 ◽  
Vol 21 (7) ◽  
pp. 2527 ◽  
Author(s):  
Qingxin Li ◽  
CongBao Kang
Keyword(s):  
Nmr Spectroscopy ◽  
Drug Design ◽  
Conformational Changes ◽  
Structural Information ◽  
Protein Structures ◽  
Rational Drug Design ◽  
Solution Nmr ◽  
Nmr Studies ◽  
Structure Based Drug Design ◽  
Additional Information

Nuclear magnetic resonance (NMR) spectroscopy plays important roles in structural biology and drug discovery, as it is a powerful tool to understand protein structures, dynamics, and ligand binding under physiological conditions. The protease of flaviviruses is an attractive target for developing antivirals because it is essential for the maturation of viral proteins. High-resolution structures of the proteases in the absence and presence of ligands/inhibitors were determined using X-ray crystallography, providing structural information for rational drug design. Structural studies suggest that proteases from Dengue virus (DENV), West Nile virus (WNV), and Zika virus (ZIKV) exist in open and closed conformations. Solution NMR studies showed that the closed conformation is predominant in solution and should be utilized in structure-based drug design. Here, we reviewed solution NMR studies of the proteases from these viruses. The accumulated studies demonstrated that NMR spectroscopy provides additional information to understand conformational changes of these proteases in the absence and presence of substrates/inhibitors. In addition, NMR spectroscopy can be used for identifying fragment hits that can be further developed into potent protease inhibitors.

Blind Man’s Bluff – Elaboration of Fragment Hits in the Absence of Structure for the Development of Antitrypsin Deficiency Inhibitors

2013 ◽  
Vol 66 (12) ◽  
pp. 1525 ◽  
Author(s):  
Stephen J. Headey ◽  
Mary C. Pearce ◽  
Martin J. Scanlon ◽  
Stephen P. Bottomley
Keyword(s):  
Nmr Spectroscopy ◽  
Protein Binding ◽  
Protein Misfolding ◽  
Structural Information ◽  
Rational Drug Design ◽  
Information Need ◽  
X Ray Crystallography ◽  
Rational Drug ◽  
Fragment Library ◽  
Antitrypsin Deficiency

The three pillars of rational drug design from a fragment library are an efficient screen, a robust assay, and atomic-resolution structures of the protein–ligand complexes. However, not all targets are amenable to structure determination by X-ray crystallography or NMR spectroscopy. In particular, targets involved in diseases of protein misfolding are inherently intractable. In the absence of structures, we are blind. However, the lack of structural information need not preclude the use of fragment-based approaches. The use of appropriate NMR techniques can enable us to detect the effects of protein binding on ligand resonances. In our efforts to identify compounds that affect the kinetics of α1-antitrypsin misfolding, we have used saturation transfer difference NMR spectroscopy to detect hits from mixtures of compounds in a fragment library. In the absence of structures, the initial challenge is three-fold: to (1) distinguish between binding sites; (2) evaluate the relative affinities of hits; and (3) advance them to the stage where activity can be detected in biological assays. We largely achieved these aims by the use of Carr–Purcell–Meiboom–Gill NMR competition experiments that detect differential relaxation of the ligand on protein binding.

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