Indirect Covariance NMR Spectroscopy

Zhang, Fengli; Brüschweiler, Rafael

doi:10.1021/ja047241h

Cited by 137 publications

(170 citation statements)

References 8 publications

Supporting

Mentioning

169

Contrasting

Order By: Relevance

“…The peak assignment was taken from the literature (13,20). The two-dimensional 13 C-13 C proton-driven spin exchange spectra were acquired with a mixing time of 600 ms and covariance-processed (26). A total of 64 complex data points were acquired in the indirect dimension at a spectral width of 190 ppm.…”

Section: Methodsmentioning

confidence: 99%

Solid-state NMR Reveals a Close Structural Relationship between Amyloid-β Protofibrils and Oligomers

Scheidt

Morgado

Huster

2012

Journal of Biological Chemistry

View full text Add to dashboard Cite

Background: Little tertiary structure information is available for the toxic intermediates in the amyloid-␤ (A␤) fibrillation process. Results: A␤ protofibrils show tertiary contacts between Glu-22 and Ile-31, which are not present in mature fibrils. Conclusion: A␤ protofibrils share tertiary structure features with oligomers but not with mature fibrils. Significance: A␤ protofibrils must undergo a major structural reorientation in the development of mature A␤ fibrils.We have studied tertiary contacts in protofibrils and mature fibrils of amyloid-␤ (A␤) peptides using solid-state NMR spectroscopy. Although intraresidue contacts between Glu-22 and Ile-31 were found in A␤ protofibrils, these contacts were completely absent in mature A␤ fibrils. This is consistent with the current models of mature A␤ fibrils. As these intramolecular contacts have also been reported in A␤ oligomers, our measurements suggest that A␤ protofibrils are structurally more closely related to oligomers than to mature fibrils. This suggests that some structural alterations have to take place on the pathway from A␤ oligomers/protofibrils to mature fibrils, in agreement with a model that suggests a conversion of intramolecular hydrogen-bonded structures of A␤ oligomers to the intermolecular stabilized mature fibrils (Hoyer, W., Grönwall, C., Jonsson, A., Ståhl, S., and Härd, T. (2008) Proc. Natl. Acad. Sci. U.S.A. 105, 5099 -5104).Alzheimer disease is characterized by extracellular deposition of plaques of amyloid-␤ (A␤) 2 peptides in the brain (1). These protein aggregates are composed of mature A␤ fibrils, which represent the end product of a long, complex, and not well understood fibrillation process (2, 3). The fibrillation pathway initiates with soluble unstructured monomeric A␤ peptides, which are converted into oligomers, protofibrils, and finally into mature fibrils (4 -6). Recently, interest in the transient A␤ intermediate structures has been growing rapidly because these species are considered to represent the cytotoxic intermediates in Alzheimer disease (7). In addition to the well studied structure (8 -12) and dynamics (13) of mature A␤ fibrils, a growing amount of data for oligomers (14 -19) and protofibrils (20, 21) has become available. With regard to the secondary structure elements, these studies revealed that oligomers and protofibrils already exhibit the characteristic two ␤-strand sections connected by a short loop also present in mature A␤ fibrils. However, there are several significant differences between theses species. For instance, the first ␤-strand of A␤ oligomers and protofibrils is significantly shorter than that in mature A␤ fibrils and has to elongate during the conversion from protofibrils to mature fibrils (20). In addition, many questions about the tertiary structure, the fibrillation process, and the conversion from one intermediate to another are still unanswered.Härd and co-workers have resolved the structure of A␤(1-40) oligomers stabilized by an Affibody and also proposed a model for the arrangement of t...

show abstract

Section: Methodsmentioning

confidence: 99%

Solid-state NMR Reveals a Close Structural Relationship between Amyloid-β Protofibrils and Oligomers

Scheidt

Morgado

Huster

2012

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…Indirect covariance spectroscopy is a variant of covariance spectroscopy 8 -10 and was originally introduced for establishing 13 C- 13 11 Blinov et al introduced asymmetrical processing of indirect covariance spectra to eliminate potential artifacts. 12,13 The basic idea behind indirect covariance is the following.…”

Section: Methodsmentioning

confidence: 99%

“…Note that matrix F Ð F T has as its elements the dot products between rows of F and the indirect covariance transform of Eqn (1) has the effect that both frequency axes of spectrum C correspond to the indirect frequency axis ω 1 of spectrum F. 11 Therefore, the spectral resolution of C along both dimensions is determined by the spectral resolution along the indirect (ω 1 ) dimension of F. By contrast, the direct covariance spectrum 8 -10 C direct D F T Ð F 1/2 has its resolution along both dimensions determined by the resolution of F along the direct dimension ω 2 . Figure 1 compares a 2D FT NOESY spectrum of ubiquitin ( Fig.…”

Section: Methodsmentioning

confidence: 99%

Residual water suppression by indirect covariance NMR

Chen

Zhang

Brüschweiler

2007

Magnetic Reson in Chemistry

Self Cite

View full text Add to dashboard Cite

Residual water solvent signals in 2D NMR experiments adversely affect appearance and subsequent analysis of spectra. A method for water suppression that is based on indirect covariance processing is described. It produces a symmetric spectrum with a water signal that is substantially decreased or completely absent. The method, which can be combined with other water suppression schemes, is demonstrated for 2D TOCSY, NOESY, and ROESY spectra of the protein, ubiquitin in aqueous solution.

show abstract

“…The results showed that lung tissue from lung cancer patients was identified by increased incorporation of carbon from glucose into a variety of metabolites, including TCA cycle intermediates as well as nucleotides [68]. The advantage of the stable isotope-labeled NMR metabolomic approach in cancer is the chemical library of 13 C-labeled isotopes [69]including 13 C-labeled amino acids (such as glutamine, serine, and glycine [70]), 13 C-labeled acetate, and 31 P-labeled phosphorylcholine [71]-thus allowing the determination of metabolic pathways in cancer related to protein and fatty acid synthesis, nucleic acid synthesis, nucleotide synthesis, TCA cycle, and carbohydrate metabolism. It should be noted that this approach is equally applicable to MS-based approaches.…”

Section: Nmr-based Metabolomic Analysis Of Plasma/serum and Urine In mentioning

confidence: 99%

NMR-Based Metabolomics and Its Application in Drug Metabolism and Cancer Research

2016

View full text Add to dashboard Cite

Purpose of Review In this review, the contribution of NMR to the metabolomics field will be discussed-particularly as it relates to cancer and drug metabolism research. An overview of the typical NMR metabolomic experiment will be presented while emphasizing important caveats ranging from experimental design to data interpretation. Recent Findings Despite some of the drawbacks of NMR, including reduced sensitivity compared to mass spectrometry-based approaches, NMR-based metabolomic approaches have provided considerable insight into drug and cancer metabolism. Advances in flux analysis based on the strategic use of isotopes have generated unique perspectives of cancer from the cellular and tissue levels. Summary Combined with other "omics" tools, including genomics, proteomics, and transcriptomics, metabolomic analysis completes the holistic view of metabolism. Many of these NMR-based approaches are likely to find their way into the clinic and become a common diagnostic tool.

show abstract

Indirect Covariance NMR Spectroscopy

Cited by 137 publications

References 8 publications

Solid-state NMR Reveals a Close Structural Relationship between Amyloid-β Protofibrils and Oligomers

Solid-state NMR Reveals a Close Structural Relationship between Amyloid-β Protofibrils and Oligomers

Residual water suppression by indirect covariance NMR

NMR-Based Metabolomics and Its Application in Drug Metabolism and Cancer Research

Contact Info

Product

Resources

About