Dependence of Amino Acid Side Chain 13C Shifts on Dihedral Angle: Application to Conformational Analysis
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- 作者：Robert E. London ; Brett D. Wingad ; Geoffrey A. Mueller
- 刊名：Journal of the American Chemical Society
- 出版年：2008
- 出版时间：August 20, 2008
- 年：2008
- 卷：130
- 期：33
- 页码：11097-11105
- 全文大小：307K
- 年卷期：v.130,no.33(August 20, 2008)
- ISSN：1520-5126
文摘
Chemical shift data from the BiomagResDataBank and conformational data derived from the protein data bank have been correlated in order to explore the conformational dependence of side chain 13C resonance shifts. Consistent with predictions based on steric compression, upfield shifts for Cγ resonances of Thr, Val, Ile, Leu, Met, Arg, Lys, Glu, and Gln residues correlate with both the number of heavy atom (nonproton) γ-substituents and with gauche conformational orientations of γ-substituents. The 13C shift/conformation correlations are most apparent for Cγ carbons but also can be observed at positions further from the backbone. Intraresidue steric conflict leads to a correlation between upfield-shifted side chain 13C resonances and statistically lower probabilities in surveys of protein side chain conformation. Illustrative applications to the DNA pol λ lyase domain and to dihydrofolate reductase are discussed. In the latter case, 13C shift analysis indicates that the conformation of the remote residue V119 on the βF-βG loop is correlated with the redox state of the bound pyridine nucleotide cofactor, providing one basis for discrimination between substrate and product. It is anticipated that 13C shift data for protein sidechains can provide a useful basis for the analysis of conformational changes even in large, deuterated proteins. Additionally, the large dependence of the leucine methyl shift difference, δCδ1−δCδ2, on both χ1 and χ2 is sufficient to allow this parameter to be used as a restraint in structure calculations if stereospecific assignment data are available.