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Nonplanar peptide bonds in proteins are common and conserved but not biased toward active sites.

ABSTRACT: The planarity of peptide bonds is an assumption that underlies decades of theoretical modeling of proteins. Peptide bonds strongly deviating from planarity are considered very rare features of protein structure that occur for functional reasons. Here, empirical analyses of atomic-resolution protein structures reveal that trans peptide groups can vary by more than 25° from planarity and that the true extent of nonplanarity is underestimated even in 1.2 ? resolution structures. Analyses as a function of the ?,?-backbone dihedral angles show that the expected value deviates by ± 8° from planar as a systematic function of conformation, but that the large majority of variation in planarity depends on tertiary effects. Furthermore, we show that those peptide bonds in proteins that are most nonplanar, deviating by over 20° from planarity, are not strongly associated with active sites. Instead, highly nonplanar peptides are simply integral components of protein structure related to local and tertiary structural features that tend to be conserved among homologs. To account for the systematic ?,?-dependent component of nonplanarity, we present a conformation-dependent library that can be used in crystallographic refinement and predictive protein modeling.

SUBMITTER: Berkholz DS

PROVIDER: S-EPMC3258596 | biostudies-literature | 2012 Jan

REPOSITORIES: biostudies-literature

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Nonplanar peptide bonds in proteins are common and conserved but not biased toward active sites.

Berkholz Donald S DS Driggers Camden M CM Shapovalov Maxim V MV Dunbrack Roland L RL Karplus P Andrew PA

Proceedings of the National Academy of Sciences of the United States of America 20111223 2

The planarity of peptide bonds is an assumption that underlies decades of theoretical modeling of proteins. Peptide bonds strongly deviating from planarity are considered very rare features of protein structure that occur for functional reasons. Here, empirical analyses of atomic-resolution protein structures reveal that trans peptide groups can vary by more than 25° from planarity and that the true extent of nonplanarity is underestimated even in 1.2 Å resolution structures. Analyses as a funct ...[more]

PMID: 22198840

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Project description:BackgroundInsight into the function of carbohydrate-active enzymes is required to understand their biological role and industrial potential. There is a need for better use of the ample genomic data in order to enable selection of the most interesting proteins for further studies. The basis for elaborating a new approach to sequence analysis is the hypothesis that when using conserved peptide patterns to determine the similarities between proteins, the exact spacing between conserved adjacent amino acids in the proteins plays a prominent functional role. Thus, the objective of developing the method of conserved unique peptide patterns (CUPP) is to construct a peptide-based grouping and validate the method to provide evidence that CUPP captures function-related features of the individual carbohydrate-active enzymes (as defined by CAZy families). This approach facilitates grouping of enzymes at a level lower than protein families and/or subfamilies. A standardized, efficient, and robust approach to functional annotation of carbohydrate-active enzymes would support improved molecular insight into enzyme-substrate interaction.ResultsA new nonalignment-based clustering and functional annotation tool was developed that uses conserved unique peptides patterns to perform automated clustering of proteins and formation of protein groups. A peptide-based model was constructed for each of these protein CUPP groups to be used to automatically annotate protein family, subfamily, and EC function of carbohydrate-active enzymes. CUPP prediction can annotate proteins (from any CAZy family) with high F-score to existing family (0.966), subfamily (0.961), and EC-function (0.843). The speed of the CUPP program was estimated and exemplified by prediction of the 504,017 nonredundant proteins of CAZy in less than four CPU hours.ConclusionIt was possible to construct an automated system for clustering proteins within families and use the resulting CUPP groups to directly build peptide-based models for genome annotation. The CUPP runtime, F-score, sensitivity, and precisions of family and subfamily annotations match or represent an improvement compared to state-of-the-art tools. The speed of the CUPP annotation is similar to the rapid DIAMOND annotation tool. CUPP facilitates automated annotation of full genome assemblies to any CAZy family.

Dataset Information

Nonplanar peptide bonds in proteins are common and conserved but not biased toward active sites.

Publications

Nonplanar peptide bonds in proteins are common and conserved but not biased toward active sites.

Similar Datasets

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