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Deuterium isotope effects on 15N backbone chemical shifts in proteins.

Abildgaard J, Hansen PE, Manalo MN, LiWang A - J. Biomol. NMR (2009)

Bottom Line: The effect of hydrogen bonding is rationalized in part as an electric-field effect on the first derivative of the nuclear shielding with respect to N-H bond length.Another contributing factor is the effect of increased anharmonicity of the N-H stretching vibrational state upon hydrogen bonding, which results in an altered N-H/N-D equilibrium bond length ratio.For residues with uncharged side chains a very good prediction of isotope effects can be made.

View Article: PubMed Central - PubMed

Affiliation: Department of Science, Systems and Models, Roskilde University, Roskilde, Denmark.

ABSTRACT
Quantum mechanical calculations are presented that predict that one-bond deuterium isotope effects on the (15)N chemical shift of backbone amides of proteins, (1)Delta(15)N(D), are sensitive to backbone conformation and hydrogen bonding. A quantitative empirical model for (1)Delta(15)N(D) including the backbone dihedral angles, Phi and Psi, and the hydrogen bonding geometry is presented for glycine and amino acid residues with aliphatic side chains. The effect of hydrogen bonding is rationalized in part as an electric-field effect on the first derivative of the nuclear shielding with respect to N-H bond length. Another contributing factor is the effect of increased anharmonicity of the N-H stretching vibrational state upon hydrogen bonding, which results in an altered N-H/N-D equilibrium bond length ratio. The N-H stretching anharmonicity contribution falls off with the cosine of the N-H...O bond angle. For residues with uncharged side chains a very good prediction of isotope effects can be made. Thus, for proteins with known secondary structures, (1)Delta(15)N(D) can provide insights into hydrogen bonding geometries.

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The N-formyl or N-acetylaminoacidamides used in the calculations. All heavy atom torsion angles, the RN–O distance, the θC′–N···O angle and the ϕC′–N···O−C′ dihedral angle were kept at the experimental X-ray values. All other bond length and angles, and all hydrogen positions were geometry optimized at the BPW91/6-31G(d) or RHF/6-31G(d) level
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Fig1: The N-formyl or N-acetylaminoacidamides used in the calculations. All heavy atom torsion angles, the RN–O distance, the θC′–N···O angle and the ϕC′–N···O−C′ dihedral angle were kept at the experimental X-ray values. All other bond length and angles, and all hydrogen positions were geometry optimized at the BPW91/6-31G(d) or RHF/6-31G(d) level

Mentions: Deuterium isotope effects on chemical shifts have proved to be a sensitive gauge for hydrogen bonding (Jameson 1991; Abildgaard et al. 1998; Dziembowska et al. 2004; Kim et al. 2006). Deuterium substitution at the N–H hydrogen site leads to one-bond isotope effects on the 15N chemical shift: 1Δ15N(D) = σ15N(D)−σ15N(H) = δ15N(H)−δ15N(D). This “difference” is caused by a small change in the (1) vibrational state due to the altered reduced mass upon deuteriation, and (2) equilibrium geometry due to anharmonicity of the N–H stretching mode potential energy surface. Deuterium substitution is favorable for the study of isotope effects due to the large relative change in mass. 15N is a good nucleus for observation because of its large chemical shift range. 1Δ15N(D) reports on the hydrogen-bonding geometry in ammonium ions (Munch et al. 1992), and Jaravine et al. (2004) found that 1Δ15N(D) values in ubiquitin could be expressed as a linear function of the 15N chemical shift and the trans-hydrogen bond scalar coupling h3JNC′. One-bond deuterium isotope effects on 13Cα (1Δ13Cα(D)) have been shown to correlate with protein backbone conformation (LeMaster et al. 1994) and in principle can be used like 1Hα, 13Cα, and 13Cβ chemical shifts and 1JCαHα for distinguishing α-helix and β-strand secondary structures (Wishart and Case 2001). Our objective here is to demonstrate how 1Δ15N(D) is determined by protein backbone structure, and in addition by the hydrogen-bonding geometry (Fig. 1).Fig. 1


Deuterium isotope effects on 15N backbone chemical shifts in proteins.

Abildgaard J, Hansen PE, Manalo MN, LiWang A - J. Biomol. NMR (2009)

The N-formyl or N-acetylaminoacidamides used in the calculations. All heavy atom torsion angles, the RN–O distance, the θC′–N···O angle and the ϕC′–N···O−C′ dihedral angle were kept at the experimental X-ray values. All other bond length and angles, and all hydrogen positions were geometry optimized at the BPW91/6-31G(d) or RHF/6-31G(d) level
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2697368&req=5

Fig1: The N-formyl or N-acetylaminoacidamides used in the calculations. All heavy atom torsion angles, the RN–O distance, the θC′–N···O angle and the ϕC′–N···O−C′ dihedral angle were kept at the experimental X-ray values. All other bond length and angles, and all hydrogen positions were geometry optimized at the BPW91/6-31G(d) or RHF/6-31G(d) level
Mentions: Deuterium isotope effects on chemical shifts have proved to be a sensitive gauge for hydrogen bonding (Jameson 1991; Abildgaard et al. 1998; Dziembowska et al. 2004; Kim et al. 2006). Deuterium substitution at the N–H hydrogen site leads to one-bond isotope effects on the 15N chemical shift: 1Δ15N(D) = σ15N(D)−σ15N(H) = δ15N(H)−δ15N(D). This “difference” is caused by a small change in the (1) vibrational state due to the altered reduced mass upon deuteriation, and (2) equilibrium geometry due to anharmonicity of the N–H stretching mode potential energy surface. Deuterium substitution is favorable for the study of isotope effects due to the large relative change in mass. 15N is a good nucleus for observation because of its large chemical shift range. 1Δ15N(D) reports on the hydrogen-bonding geometry in ammonium ions (Munch et al. 1992), and Jaravine et al. (2004) found that 1Δ15N(D) values in ubiquitin could be expressed as a linear function of the 15N chemical shift and the trans-hydrogen bond scalar coupling h3JNC′. One-bond deuterium isotope effects on 13Cα (1Δ13Cα(D)) have been shown to correlate with protein backbone conformation (LeMaster et al. 1994) and in principle can be used like 1Hα, 13Cα, and 13Cβ chemical shifts and 1JCαHα for distinguishing α-helix and β-strand secondary structures (Wishart and Case 2001). Our objective here is to demonstrate how 1Δ15N(D) is determined by protein backbone structure, and in addition by the hydrogen-bonding geometry (Fig. 1).Fig. 1

Bottom Line: The effect of hydrogen bonding is rationalized in part as an electric-field effect on the first derivative of the nuclear shielding with respect to N-H bond length.Another contributing factor is the effect of increased anharmonicity of the N-H stretching vibrational state upon hydrogen bonding, which results in an altered N-H/N-D equilibrium bond length ratio.For residues with uncharged side chains a very good prediction of isotope effects can be made.

View Article: PubMed Central - PubMed

Affiliation: Department of Science, Systems and Models, Roskilde University, Roskilde, Denmark.

ABSTRACT
Quantum mechanical calculations are presented that predict that one-bond deuterium isotope effects on the (15)N chemical shift of backbone amides of proteins, (1)Delta(15)N(D), are sensitive to backbone conformation and hydrogen bonding. A quantitative empirical model for (1)Delta(15)N(D) including the backbone dihedral angles, Phi and Psi, and the hydrogen bonding geometry is presented for glycine and amino acid residues with aliphatic side chains. The effect of hydrogen bonding is rationalized in part as an electric-field effect on the first derivative of the nuclear shielding with respect to N-H bond length. Another contributing factor is the effect of increased anharmonicity of the N-H stretching vibrational state upon hydrogen bonding, which results in an altered N-H/N-D equilibrium bond length ratio. The N-H stretching anharmonicity contribution falls off with the cosine of the N-H...O bond angle. For residues with uncharged side chains a very good prediction of isotope effects can be made. Thus, for proteins with known secondary structures, (1)Delta(15)N(D) can provide insights into hydrogen bonding geometries.

Show MeSH
Related in: MedlinePlus