An Experimental and Theoretical Investigation of the Chemical Shielding Tensors of 13Cα of Alanine, Valine, and Leucine Residues in Solid Peptides and in Proteins in Solution

• Published in: Journal of the American Chemical Society Vol. 123; no. 42; pp. 10362 - 10369
• Main Authors: Havlin, Robert H, Laws, David D, Bitter, Hans-Marcus L, Sanders, Lori K, Sun, Haihong, Grimley, Joshua S, Wemmer, David E, Pines, Alexander, Oldfield, Eric
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 24.10.2001
• Subjects: BASIC BIOLOGICAL SCIENCES; LEUCINE; PEPTIDES; PROTEINS; RESIDUES; SHIELDING; VALINE
• ISSN: 0002-7863; 1520-5126
• DOI: 10.1021/ja0115060

We have carried out a solid-state magic-angle sample-spinning (MAS) nuclear magnetic resonance (NMR) spectroscopic investigation of the 13Cα chemical shielding tensors of alanine, valine, and leucine residues in a series of crystalline peptides of known structure. For alanine and leucine, which are not branched at the β-carbon, the experimental chemical shift anisotropy (CSA) spans (Ω) are large, about 30 ppm, independent of whether the residues adopt helical or sheet geometries, and are in generally good accord with Ω values calculated by using ab initio Hartree−Fock quantum chemical methods. The experimental Ωs for valine Cα in two peptides (in sheet geometries) are also large and in good agreement with theoretical predictions. In contrast, the “CSAs” (Δσ*) obtained from solution NMR data for alanine, valine, and leucine residues in proteins show major differences, with helical residues having Δσ* values of ∼6 ppm while sheet residues have Δσ* ≈ 27 ppm. The origins of these differences are shown to be due to the different definitions of the CSA. When defined in terms of the solution NMR CSA, the solid-state results also show small helical but large sheet CSA values. These results are of interest since they lead to the idea that only the β-branched amino acids threonine, valine, and isoleucine can have small (static) tensor spans, Ω (in helical geometries), and that the small helical “CSAs” seen in solution NMR are overwhelmingly dominated by changes in tensor orientation, from sheet to helix. These results have important implications for solid-state NMR structural studies which utilize the CSA span, Ω, to differentiate between helical and sheet residues. Specifically, there will be only a small degree of spectral editing possible in solid proteins since the spans, Ω, for the dominant nonbranched amino acids are quite similar. Editing on the basis of Ω will, however, be very effective for many Thr, Val, and Ileu residues, which frequently have small (∼15−20 ppm) helical CSA (Ω) spans.