Context-Independent, Temperature-Dependent Helical Propensities for Amino Acid Residues

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• 作者：Robert J. Moreau ; Christian R. Schubert ; Khaled A. Nasr ; Marianna Trk ; Justin S. Miller ; Robert J. Kennedy ; Daniel S. Kemp
• 刊名：Journal of the American Chemical Society
• 出版年：2009
• 出版时间：September 16, 2009
• 年：2009
• 卷：131
• 期：36
• 页码：13107-13116
• 全文大小：396K
• 年卷期：v.131,no.36(September 16, 2009)
• ISSN：1520-5126

文摘

Assigned from data sets measured in water at 2, 25, and 60 °C containing ¹³C═O NMR chemical shifts and [θ]₂₂₂ ellipticities, helical propensities are reported for the 20 genetically coded amino acids, as well as for norvaline and norleucine. These have been introduced by chemical synthesis at central sites within length-optimized, spaced, solubilized Ala₁₉ hosts. The resulting polyalanine-derived, quantitative propensity sets express for each residue its temperature-dependent but context-independent tendency to forego a coil state and join a preexisting helical conformation. At 2 °C their rank ordering is: P G < H < C, T, N < S < Y, F, W < V, D < K < Q < I < R, M < L < E < A; at 60 °C the rank becomes: H, P < G < C < R, K < T, Y, F < N, V < S < Q < W, D < I, M < E < A < L. The ΔΔG values, kcal/mol, relative to alanine, for the cluster T, N, S, Y, F, W, V, D, Q, imply that at 2 °C all are strong breakers: ΔΔG_mean = +0.63 ± 0.11, but at 60 °C their breaking tendencies are dramatically attenuated and converge toward the mean: ΔΔG_mean = +0.25 ± 0.07. Accurate modeling of helix-rich proteins found in thermophiles, mesophiles, and organisms that flourish near 0 °C thus requires appropriately matched propensity sets. Comparisons are offered between the temperature-dependent propensity assignments of this study and those previously assigned by the Scheraga group; the special problems that attend propensity assignments for charged residues are illustrated by lysine guest data; and comparisons of errors in helicity assignments from shifts and ellipticity data show that the former provide superior precision and accuracy.