Progress in Our Understanding of 19F Chemical Shifts

Dahanayake, Jayangika Niroshani; Kasireddy, Chandana; Karnes, Joseph P.; Verma, Rajni; Steinert, Ryan M.; Hildebrandt, Derek; Hull, Olivia A.; Ellis, J. Michael; Mitchell-Koch, Katie R.

doi:10.1016/bs.arnmr.2017.08.002

Cited by 29 publications

(30 citation statements)

References 220 publications

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“…Hoeltzli and Frieden observed conformational changes in dihydrofolate reductase using 19 F NMR spectroscopy (Hoeltzli and Frieden, 1998 ). The extreme sensitivity of 19 F resonance to its non-bonded environment leads 19 F NMR to provide details regarding protein conformational changes with rapid data acquisition and no heavy isotope labeling (Dahanayake et al, 2018 ).…”

Section: Discussionmentioning

confidence: 99%

How Does Solvation Layer Mobility Affect Protein Structural Dynamics?

Dahanayake

Mitchell-Koch

2018

Front. Mol. Biosci.

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Solvation is critical for protein structural dynamics. Spectroscopic studies have indicated relationships between protein and solvent dynamics, and rates of gas binding to heme proteins in aqueous solution were previously observed to depend inversely on solution viscosity. In this work, the solvent-compatible enzyme Candida antarctica lipase B, which functions in aqueous and organic solvents, was modeled using molecular dynamics simulations. Data was obtained for the enzyme in acetonitrile, cyclohexane, n-butanol, and tert-butanol, in addition to water. Protein dynamics and solvation shell dynamics are characterized regionally: for each α-helix, β-sheet, and loop or connector region. Correlations are seen between solvent mobility and protein flexibility. So, does local viscosity explain the relationship between protein structural dynamics and solvation layer dynamics? Halle and Davidovic presented a cogent analysis of data describing the global hydrodynamics of a protein (tumbling in solution) that fits a model in which the protein's interfacial viscosity is higher than that of bulk water's, due to retarded water dynamics in the hydration layer (measured in NMR τ2 reorientation times). Numerous experiments have shown coupling between protein and solvation layer dynamics in site-specific measurements. Our data provides spatially-resolved characterization of solvent shell dynamics, showing correlations between regional solvation layer dynamics and protein dynamics in both aqueous and organic solvents. Correlations between protein flexibility and inverse solvent viscosity (1/η) are considered across several protein regions and for a rather disparate collection of solvents. It is seen that the correlation is consistently higher when local solvent shell dynamics are considered, rather than bulk viscosity. Protein flexibility is seen to correlate best with either the local interfacial viscosity or the ratio of the mobility of an organic solvent in a regional solvation layer relative to hydration dynamics around the same region. Results provide insight into the function of aqueous proteins, while also suggesting a framework for interpreting and predicting enzyme structural dynamics in non-aqueous solvents, based on the mobility of solvents within the solvation layer. We suggest that Kramers' theory may be used in future work to model protein conformational transitions in different solvents by incorporating local viscosity effects.

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Section: Discussionmentioning

confidence: 99%

How Does Solvation Layer Mobility Affect Protein Structural Dynamics?

Dahanayake

Mitchell-Koch

2018

Front. Mol. Biosci.

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“…Intuitively, the largest chemical shift perturbations are expected to be seen for residues in the closest proximity to the bound ligand. An additional advantage of this method is that signal acquisition in these experiments is typically rapid, as large signal-to-noise ratios are not needed to obtain precise indication of the positive presence of binding interactions [ 33 ].…”

Section: Reviewmentioning

confidence: 99%

¹⁹F NMR as a tool in chemical biology

Giménez¹,

Phelan²,

Murphy³

et al. 2021

Beilstein J. Org. Chem.

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We previously reviewed the use of 19F NMR in the broad field of chemical biology [Cobb, S. L.; Murphy, C. D. J. Fluorine Chem. 2009, 130, 132–140] and present here a summary of the literature from the last decade that has the technique as the central method of analysis. The topics covered include the synthesis of new fluorinated probes and their incorporation into macromolecules, the application of 19F NMR to monitor protein–protein interactions, protein–ligand interactions, physiologically relevant ions and in the structural analysis of proteins and nucleic acids. The continued relevance of the technique to investigate biosynthesis and biodegradation of fluorinated organic compounds is also described.

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“…Such modifications are achievable by making Fmoc/Boc protected 4substituted Pro analogs using Hyp in solution phase and incorporating them into peptides via standard solution-phase or solid-phase peptide synthesis protocols or even more enticingly, via the alluring "proline editing" (Thomas et al 2005;Pandey et al 2013) method on a pre-synthesized sequence on resin. Coupled with the increasing interest in 19 F NMR (Dorai 2015;Dahanayake et al 2018) and a promising future of 19 F MRI (Dahanayake et al 2018;Rose-Sperling et al 2019) probes, 4-fluoroprolines, or fluorine-containing proline analogs in general, have justifiably dominated research in chemical biology. Recently, the impact of conformationally defined 4-fluoroprolines and other fluorine containing proline analogs on peptide structure and their application as 19 F NMR probes were comprehensively reviewed (Verhoork et al 2018).…”

Section: Introductionmentioning

confidence: 99%

Conformational landscape of substituted prolines

Ganguly

Basu

2020

Biophys Rev

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The cyclic side chain of the amino acid proline confers unique conformational restraints on its backbone and side chain dihedral angles. This affects two equilibria-one at the backbone (cis/trans) and the other at the side chain (endo/exo). Substitutions on the proline ring impose additional steric and stereoelectronic effects that can further modulate both these equilibria, which in turn can also affect the backbone dihedral angle (ϕ, ψ) preferences. In this review, we have explored the conformational landscape of several termini capped mono-(2-, 3-, 4-, and 5-) substituted proline derivatives in the Cambridge Structural Database, correlating observed conformations with the nature of substituents and deciphering the underlying interactions for the observed structural biases. The impact of incorporating these derivatives within model peptides and proteins are also discussed for selected cases. Several of these substituents have been used to introduce bioorthogonal functionality and modulate structure-specific ligand recognition or used as spectroscopic probes. The incorporation of these diversely applicable functional groups, coupled with their ability to define an amino acid conformation via stereoelectronic effects, have a broad appeal among chemical biologists, molecular biophysicists, and medicinal chemists.

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Progress in Our Understanding of 19F Chemical Shifts

Cited by 29 publications

References 220 publications

How Does Solvation Layer Mobility Affect Protein Structural Dynamics?

How Does Solvation Layer Mobility Affect Protein Structural Dynamics?

¹⁹F NMR as a tool in chemical biology

Conformational landscape of substituted prolines

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Progress in Our Understanding of 19F Chemical Shifts

Cited by 29 publications

References 220 publications

How Does Solvation Layer Mobility Affect Protein Structural Dynamics?

How Does Solvation Layer Mobility Affect Protein Structural Dynamics?

19F NMR as a tool in chemical biology

Conformational landscape of substituted prolines

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Product

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¹⁹F NMR as a tool in chemical biology