1H, 13C and 15N random coil NMR chemical shifts of the common amino acids. I. Investigations of nearest-neighbor effects

Abstract

In this study we report on the 1H, 13C and 15N NMR chemical shifts for the random coil state and nearest-neighbor sequence effects measured from the protected linear hexapeptide Gly-Gly-X-Y-Gly-Gly (where X and Y are any of the 20 common amino acids). We present data for a set of 40 peptides (of the possible 400) including Gly-Gly-X-Ala-Gly-Gly and Gly-Gly-X-Pro-Gly-Gly, measured under identical aqueous conditions. Because all spectra were collected under identical experimental conditions, the data from the Gly-Gly-X-Ala-Gly-Gly series provide a complete and internally consistent set of 1H, 13C and 15N random coil chemical shifts for all 20 common amino acids. In addition, studies were also conducted into nearest-neighbor effects on the random coil shift arising from a variety of X and Y positional substitutions. Comparisons between the chemical shift measurements obtained from Gly-Gly-X-Ala-Gly-Gly and Gly-Gly-X-Pro-Gly-Gly reveal significant systematic shift differences arising from the presence of proline in the peptide sequence. Similarly, measurements of the chemical shift changes occurring for both alanine and proline (i.e., the residues in the Y position) are found to depend strongly on the type of amino acid substituted into the X position. These data lend support to the hypothesis that sequence effects play a significant role in determining peptide and protein chemical shifts.

The serum albumin‐binding domain of streptococcal protein G is a three‐helical bundle: a heteronuclear NMR study

“…When the random-coil values of the C a and C ~ nuclei for each amino-acid residue type [46] are subtracted from the chemical shifts of these nuclei in the residues of the sequence, the remainder (the secondary chemical shift) shows a characteristic pattern which allows an accurate delineation of the secondary structure in terms of a-helix, fl-strand or random coil [47]. To obtain further data on the secondary structure, the simultaneous ~SN-and L3C-edited 3D NOESYwas investigated for the presence of sequential and short-range NOEs indicative of secondary structure.…”

“…In addition, also the *Corresponding author. Fax: (46) (8) 6954084. structures of SPG immunoglobulin-binding domains in complex with Fab [18] or Fc [19] have been described. The structure of an individual domain consists of a mixed parallel/antiparallel fl-sheet of four strands, with a single c~-helix packed onto the sheet.…”

Effect of pH, urea, peptide length, and neighboring amino acids on alanine α‐proton random coil chemical shifts

“…(In previous model systems this was also accounted for by capping the N and C-termini. 19,22 ) The current model system incorporates two buffering amino acids on either side of the alanine. That the terminal amino acids effectively absorb the protonation/deprotonation pH effects is evidenced by the fact that the -proton chemical shift of alanine did not significantly change for any of the peptides over the pH range studied ( 0.02 ppm).…”

“…Several studies have been done to measure the -proton random coil chemical shift value for each of the 20 common amino acids, and while there is general agreement among the studies, there are some notable discrepancies. 6,[18][19][20][21][22][23][24][25] For instance, in four separate studies the histidine random coil chemical shift value has been determined to be 4.630 ppm (pH 7, no urea, 358C, GGX aa A), 18 4.73 ppm (pH 5, 1M urea, 258C, GGX aa AGG, termini protected), 19 4.77 ppm (pH 5, no urea, 48C, GGX aa GG), 20 and 4.79 ppm (pH 2.3, 8M urea, 208C, GGX aa GG, termini protected). 22 Variations in the model systems (peptide length, free vs. capped termini) and the solution environment (pH, urea and temperature) are possible explanations for the different values observed.…”

“…To further complicate matters, studies have also shown that neighboring amino acids can affect the -proton random coil chemical shift value of an amino acid. 19,[23][24][25] Groups studying -hairpin structure have resorted to synthesizing at least two peptides for each hairpin studied, one with -hairpin structure and a control peptide of similar sequence with no hairpin structure, to account for the shift effects of neighboring amino acids. [9][10][11][12][13][14] In the current study it is our goal to add to the collective knowledge of chemical shift effects and correction factors by systematically studying the effect of solution environments (pH, urea) and molecular environments (peptide length, free vs. capped termini, and neighboring amino acids) on -proton chemical shifts.…”