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
Potential n→π* interactions in the selectivity filter of the KcsA potassium ion channelA single chain of the tetrameric channel determined at a high K+ concentration (PDB code 1k4c) structure was superposed on that determined at a low K+ concentration (PDB code 1k4d). Superpositions were carried out by the Secondary Structure Matching service at EBI (http://www.ebi.ac.uk/msd-srv/ssm).
© Copyright Policy
Related In: Results  -  Collection

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

Figure 5: Potential n→π* interactions in the selectivity filter of the KcsA potassium ion channelA single chain of the tetrameric channel determined at a high K+ concentration (PDB code 1k4c) structure was superposed on that determined at a low K+ concentration (PDB code 1k4d). Superpositions were carried out by the Secondary Structure Matching service at EBI (http://www.ebi.ac.uk/msd-srv/ssm).

Mentions: We searched the PDB for runs of four or more n→π* interactions not contained within common secondary structural elements in proteins. This search returned only eight hits from a possible 7833 sets of four residues. Detailed examination showed that these hits were located between α-helices or β-strands, except for one that formed part of an iron-binding site (residues 246–251 inclusive in cytosine deaminase, PDB code 1ra0 22, of which His246 is a ligand to the iron ion). Most notably, however, in a wider search of the PDB, we found a run of four n→π* interactions in the selectivity filter of the potassium ion channel from Streptomyces lividans (KcsA; Fig. 5)23, while n→π* interactions were nearly absent in the structure of the filter region determined at high K+ concentration.


n-->pi* interactions in proteins.

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

Potential n→π* interactions in the selectivity filter of the KcsA potassium ion channelA single chain of the tetrameric channel determined at a high K+ concentration (PDB code 1k4c) structure was superposed on that determined at a low K+ concentration (PDB code 1k4d). Superpositions were carried out by the Secondary Structure Matching service at EBI (http://www.ebi.ac.uk/msd-srv/ssm).
© Copyright Policy
Related In: Results  -  Collection

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

Figure 5: Potential n→π* interactions in the selectivity filter of the KcsA potassium ion channelA single chain of the tetrameric channel determined at a high K+ concentration (PDB code 1k4c) structure was superposed on that determined at a low K+ concentration (PDB code 1k4d). Superpositions were carried out by the Secondary Structure Matching service at EBI (http://www.ebi.ac.uk/msd-srv/ssm).
Mentions: We searched the PDB for runs of four or more n→π* interactions not contained within common secondary structural elements in proteins. This search returned only eight hits from a possible 7833 sets of four residues. Detailed examination showed that these hits were located between α-helices or β-strands, except for one that formed part of an iron-binding site (residues 246–251 inclusive in cytosine deaminase, PDB code 1ra0 22, of which His246 is a ligand to the iron ion). Most notably, however, in a wider search of the PDB, we found a run of four n→π* interactions in the selectivity filter of the potassium ion channel from Streptomyces lividans (KcsA; Fig. 5)23, while n→π* interactions were nearly absent in the structure of the filter region determined at high K+ concentration.

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