Limits...
n-->pi* interactions in proteins.

Bartlett GJ, Choudhary A, Raines RT, Woolfson DN - Nat. Chem. Biol. (2010)

Bottom Line: Natural bond orbital analysis predicted significant n-->pi* interactions in certain regions of the Ramachandran plot.Moreover, the n-->pi* interactions are abundant and especially prevalent in common secondary structures such as alpha-, 3(10)- and polyproline II helices and twisted beta-sheets.In addition to their evident effects on protein structure and stability, n-->pi* interactions could have important roles in protein folding and function, and merit inclusion in computational force fields.

View Article: PubMed Central - PubMed

Affiliation: School of Chemistry, University of Bristol, Bristol, United Kingdom.

ABSTRACT
Hydrogen bonds between backbone amides are common in folded proteins. Here, we show that an intimate interaction between backbone amides also arises from the delocalization of a lone pair of electrons (n) from an oxygen atom to the antibonding orbital (pi*) of the subsequent carbonyl group. Natural bond orbital analysis predicted significant n-->pi* interactions in certain regions of the Ramachandran plot. These predictions were validated by a statistical analysis of a large, non-redundant subset of protein structures determined to high resolution. The correlation between these two independent studies is striking. Moreover, the n-->pi* interactions are abundant and especially prevalent in common secondary structures such as alpha-, 3(10)- and polyproline II helices and twisted beta-sheets. In addition to their evident effects on protein structure and stability, n-->pi* interactions could have important roles in protein folding and function, and merit inclusion in computational force fields.

Show MeSH

Related in: MedlinePlus

Histograms of d and θ values for Xaa–Ala, Xaa–Gly, and Xaa–Pro dipeptides in α-helices, β-sheets, and PII helicesMean values (± SD) of d and θ were as follows. α-Helix: Xaa–Ala, d = 2.97 ± 0.10 Å, θ = 102.9 ± 4.7°; Xaa–Gly, d = 3.01 ± 0.17 Å, θ = 103.0 ± 7.6°; Xaa–Pro, d = 2.89 ± 0.10 Å, θ = 107.2 ± 6.5°. β-Sheet: Xaa–Ala, d = 3.87 ± 0.32 Å, θ = 118.1 ± 9.3°; Xaa–Gly, d = 3.89 ± 0.36 Å, θ = 112.7 ± 11.3°; Xaa–Pro, d = 3.17 ± 0.33 Å, θ = 103.8 ± 13.5°. PII helix: Xaa–Ala, d = 3.16 ± 0.33 Å, θ = 97.7 ± 9.5°; Xaa–Pro, d = 3.01 ± 0.21 Å, θ = 95.6 ± 8.7°. Mean values of d for Xaa–Pro were smaller than those for Xaa–Ala and Xaa–Gly in each secondary structure, according to Student’s t-test (p < 0.05, one-tailed test, number of observations as in Table 1). Mean values of θ for Xaa–Pro were larger than those for Xaa–Ala and Xaa–Gly in α-helices, but smaller than those for Xaa–Ala and Xaa–Gly in β-sheets, according to Student’s t-test (p < 0.05, one-tailed test, number of observations as in Table 1). The number of Xaa–Gly dipeptides in PII helices was too small for their inclusion.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC2921280&req=5

Figure 3: Histograms of d and θ values for Xaa–Ala, Xaa–Gly, and Xaa–Pro dipeptides in α-helices, β-sheets, and PII helicesMean values (± SD) of d and θ were as follows. α-Helix: Xaa–Ala, d = 2.97 ± 0.10 Å, θ = 102.9 ± 4.7°; Xaa–Gly, d = 3.01 ± 0.17 Å, θ = 103.0 ± 7.6°; Xaa–Pro, d = 2.89 ± 0.10 Å, θ = 107.2 ± 6.5°. β-Sheet: Xaa–Ala, d = 3.87 ± 0.32 Å, θ = 118.1 ± 9.3°; Xaa–Gly, d = 3.89 ± 0.36 Å, θ = 112.7 ± 11.3°; Xaa–Pro, d = 3.17 ± 0.33 Å, θ = 103.8 ± 13.5°. PII helix: Xaa–Ala, d = 3.16 ± 0.33 Å, θ = 97.7 ± 9.5°; Xaa–Pro, d = 3.01 ± 0.21 Å, θ = 95.6 ± 8.7°. Mean values of d for Xaa–Pro were smaller than those for Xaa–Ala and Xaa–Gly in each secondary structure, according to Student’s t-test (p < 0.05, one-tailed test, number of observations as in Table 1). Mean values of θ for Xaa–Pro were larger than those for Xaa–Ala and Xaa–Gly in α-helices, but smaller than those for Xaa–Ala and Xaa–Gly in β-sheets, according to Student’s t-test (p < 0.05, one-tailed test, number of observations as in Table 1). The number of Xaa–Gly dipeptides in PII helices was too small for their inclusion.

Mentions: We examined in detail the Oi–1···Ci distance (d, Fig. 2a) as well as the Oi–1···Ci=Oi angle (θ, Fig. 2a) for Xaa–Pro, Xaa–Gly, and Xaa–Ala dipeptides in protein structures. For α-helices, β-strands, PII helices, and runs of residues with no secondary structure, we found that the mean Oi–1···Ci distance in Xaa–Pro was shorter by ~0.1 Å than the same distance in Xaa–Gly and Xaa–Ala (Fig. 3). In α-helices, the mean Oi-1···Ci=Oi angle was 107.2° ± 6.5° for Xaa–Pro motifs, compared with 103.0° ± 7.6° for Xaa-Gly and 102.9° ± 4.6° for Xaa–Ala. This wider angle is close to the Bürgi–Dunitz trajectory. In β-strands, the mean Oi-1···Ci=Oi angle was 103.8° ± 13.5° for Xaa–Pro, compared with 118.1° ± 9.3° for Xaa–Ala and 112.7° ± 11.3° for Xaa–Gly.


n-->pi* interactions in proteins.

Bartlett GJ, Choudhary A, Raines RT, Woolfson DN - Nat. Chem. Biol. (2010)

Histograms of d and θ values for Xaa–Ala, Xaa–Gly, and Xaa–Pro dipeptides in α-helices, β-sheets, and PII helicesMean values (± SD) of d and θ were as follows. α-Helix: Xaa–Ala, d = 2.97 ± 0.10 Å, θ = 102.9 ± 4.7°; Xaa–Gly, d = 3.01 ± 0.17 Å, θ = 103.0 ± 7.6°; Xaa–Pro, d = 2.89 ± 0.10 Å, θ = 107.2 ± 6.5°. β-Sheet: Xaa–Ala, d = 3.87 ± 0.32 Å, θ = 118.1 ± 9.3°; Xaa–Gly, d = 3.89 ± 0.36 Å, θ = 112.7 ± 11.3°; Xaa–Pro, d = 3.17 ± 0.33 Å, θ = 103.8 ± 13.5°. PII helix: Xaa–Ala, d = 3.16 ± 0.33 Å, θ = 97.7 ± 9.5°; Xaa–Pro, d = 3.01 ± 0.21 Å, θ = 95.6 ± 8.7°. Mean values of d for Xaa–Pro were smaller than those for Xaa–Ala and Xaa–Gly in each secondary structure, according to Student’s t-test (p < 0.05, one-tailed test, number of observations as in Table 1). Mean values of θ for Xaa–Pro were larger than those for Xaa–Ala and Xaa–Gly in α-helices, but smaller than those for Xaa–Ala and Xaa–Gly in β-sheets, according to Student’s t-test (p < 0.05, one-tailed test, number of observations as in Table 1). The number of Xaa–Gly dipeptides in PII helices was too small for their inclusion.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2921280&req=5

Figure 3: Histograms of d and θ values for Xaa–Ala, Xaa–Gly, and Xaa–Pro dipeptides in α-helices, β-sheets, and PII helicesMean values (± SD) of d and θ were as follows. α-Helix: Xaa–Ala, d = 2.97 ± 0.10 Å, θ = 102.9 ± 4.7°; Xaa–Gly, d = 3.01 ± 0.17 Å, θ = 103.0 ± 7.6°; Xaa–Pro, d = 2.89 ± 0.10 Å, θ = 107.2 ± 6.5°. β-Sheet: Xaa–Ala, d = 3.87 ± 0.32 Å, θ = 118.1 ± 9.3°; Xaa–Gly, d = 3.89 ± 0.36 Å, θ = 112.7 ± 11.3°; Xaa–Pro, d = 3.17 ± 0.33 Å, θ = 103.8 ± 13.5°. PII helix: Xaa–Ala, d = 3.16 ± 0.33 Å, θ = 97.7 ± 9.5°; Xaa–Pro, d = 3.01 ± 0.21 Å, θ = 95.6 ± 8.7°. Mean values of d for Xaa–Pro were smaller than those for Xaa–Ala and Xaa–Gly in each secondary structure, according to Student’s t-test (p < 0.05, one-tailed test, number of observations as in Table 1). Mean values of θ for Xaa–Pro were larger than those for Xaa–Ala and Xaa–Gly in α-helices, but smaller than those for Xaa–Ala and Xaa–Gly in β-sheets, according to Student’s t-test (p < 0.05, one-tailed test, number of observations as in Table 1). The number of Xaa–Gly dipeptides in PII helices was too small for their inclusion.
Mentions: We examined in detail the Oi–1···Ci distance (d, Fig. 2a) as well as the Oi–1···Ci=Oi angle (θ, Fig. 2a) for Xaa–Pro, Xaa–Gly, and Xaa–Ala dipeptides in protein structures. For α-helices, β-strands, PII helices, and runs of residues with no secondary structure, we found that the mean Oi–1···Ci distance in Xaa–Pro was shorter by ~0.1 Å than the same distance in Xaa–Gly and Xaa–Ala (Fig. 3). In α-helices, the mean Oi-1···Ci=Oi angle was 107.2° ± 6.5° for Xaa–Pro motifs, compared with 103.0° ± 7.6° for Xaa-Gly and 102.9° ± 4.6° for Xaa–Ala. This wider angle is close to the Bürgi–Dunitz trajectory. In β-strands, the mean Oi-1···Ci=Oi angle was 103.8° ± 13.5° for Xaa–Pro, compared with 118.1° ± 9.3° for Xaa–Ala and 112.7° ± 11.3° for Xaa–Gly.

Bottom Line: Natural bond orbital analysis predicted significant n-->pi* interactions in certain regions of the Ramachandran plot.Moreover, the n-->pi* interactions are abundant and especially prevalent in common secondary structures such as alpha-, 3(10)- and polyproline II helices and twisted beta-sheets.In addition to their evident effects on protein structure and stability, n-->pi* interactions could have important roles in protein folding and function, and merit inclusion in computational force fields.

View Article: PubMed Central - PubMed

Affiliation: School of Chemistry, University of Bristol, Bristol, United Kingdom.

ABSTRACT
Hydrogen bonds between backbone amides are common in folded proteins. Here, we show that an intimate interaction between backbone amides also arises from the delocalization of a lone pair of electrons (n) from an oxygen atom to the antibonding orbital (pi*) of the subsequent carbonyl group. Natural bond orbital analysis predicted significant n-->pi* interactions in certain regions of the Ramachandran plot. These predictions were validated by a statistical analysis of a large, non-redundant subset of protein structures determined to high resolution. The correlation between these two independent studies is striking. Moreover, the n-->pi* interactions are abundant and especially prevalent in common secondary structures such as alpha-, 3(10)- and polyproline II helices and twisted beta-sheets. In addition to their evident effects on protein structure and stability, n-->pi* interactions could have important roles in protein folding and function, and merit inclusion in computational force fields.

Show MeSH
Related in: MedlinePlus