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Pattern similarity study of functional sites in protein sequences: lysozymes and cystatins.

Nakai S, Li-Chan EC, Dou J - BMC Biochem. (2005)

Bottom Line: Hydrogen bonding was used as the side-chain property for searching the binding sites of lysozymes.Pattern similarity and average index values of structure-related properties of side chains in short segments of three residues or longer were, for the first time, successfully applied for predicting functional sites in sequences.This new approach may be applicable to studying functional sites in un-annotated proteins, for which complete 3D structures are not yet available.

View Article: PubMed Central - HTML - PubMed

Affiliation: Food, Nutrition and Health, The University of British Columbia, 6650 Marine Drive, Vancouver, B.C., Canada. shuryo.nakai@ubc.ca

ABSTRACT

Background: Although it is generally agreed that topography is more conserved than sequences, proteins sharing the same fold can have different functions, while there are protein families with low sequence similarity. An alternative method for profile analysis of characteristic conserved positions of the motifs within the 3D structures may be needed for functional annotation of protein sequences. Using the approach of quantitative structure-activity relationships (QSAR), we have proposed a new algorithm for postulating functional mechanisms on the basis of pattern similarity and average of property values of side-chains in segments within sequences. This approach was used to search for functional sites of proteins belonging to the lysozyme and cystatin families.

Results: Hydrophobicity and beta-turn propensity of reference segments with 3-7 residues were used for the homology similarity search (HSS) for active sites. Hydrogen bonding was used as the side-chain property for searching the binding sites of lysozymes. The profiles of similarity constants and average values of these parameters as functions of their positions in the sequences could identify both active and substrate binding sites of the lysozyme of Streptomyces coelicolor, which has been reported as a new fold enzyme (Cellosyl). The same approach was successfully applied to cystatins, especially for postulating the mechanisms of amyloidosis of human cystatin C as well as human lysozyme.

Conclusion: Pattern similarity and average index values of structure-related properties of side chains in short segments of three residues or longer were, for the first time, successfully applied for predicting functional sites in sequences. This new approach may be applicable to studying functional sites in un-annotated proteins, for which complete 3D structures are not yet available.

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PCS scattergram of lysozyme families (C-, G-, V-, and CH-types) when hydrophobicity was used as property index. Hen lysozyme was used as the reference with [coefficient of determination] = 1.0 and [slope] = 1.0.
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Figure 1: PCS scattergram of lysozyme families (C-, G-, V-, and CH-types) when hydrophobicity was used as property index. Hen lysozyme was used as the reference with [coefficient of determination] = 1.0 and [slope] = 1.0.

Mentions: Figure 1 shows a scattergram derived from principal components similarity (PCS) analysis of 25 lysozyme sequences using the hydrophobicity index of side chains and hen lysozyme as a reference. A scattergram similar to this figure was also obtained when a charge index was used (instead of the hydrophobicity index) for classification. CH-type lysozymes used herein were from a fungus and Streptomyces globisporus. The v-type lysozymes were T4 and PA2 phage lysozymes, while g-type lysozymes were from goose, black swan, cassowary, ostrich and chicken G. Sixteen lysozymes (chicken C, human, horse, dog, rat, mouse, red deer, rainbow trout, pigeon, turkey, duck, California quail, Japanese quail, common bobwhite, fruit fly Drosophila, and tobacco hornworm) belong to the c-type family. The large deviations in slope (about 2) of CH-type lysozymes as seen in Figure 1 are suggestive of explicit difference in their molecular structures from those of other lysozyme types.


Pattern similarity study of functional sites in protein sequences: lysozymes and cystatins.

Nakai S, Li-Chan EC, Dou J - BMC Biochem. (2005)

PCS scattergram of lysozyme families (C-, G-, V-, and CH-types) when hydrophobicity was used as property index. Hen lysozyme was used as the reference with [coefficient of determination] = 1.0 and [slope] = 1.0.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC1173080&req=5

Figure 1: PCS scattergram of lysozyme families (C-, G-, V-, and CH-types) when hydrophobicity was used as property index. Hen lysozyme was used as the reference with [coefficient of determination] = 1.0 and [slope] = 1.0.
Mentions: Figure 1 shows a scattergram derived from principal components similarity (PCS) analysis of 25 lysozyme sequences using the hydrophobicity index of side chains and hen lysozyme as a reference. A scattergram similar to this figure was also obtained when a charge index was used (instead of the hydrophobicity index) for classification. CH-type lysozymes used herein were from a fungus and Streptomyces globisporus. The v-type lysozymes were T4 and PA2 phage lysozymes, while g-type lysozymes were from goose, black swan, cassowary, ostrich and chicken G. Sixteen lysozymes (chicken C, human, horse, dog, rat, mouse, red deer, rainbow trout, pigeon, turkey, duck, California quail, Japanese quail, common bobwhite, fruit fly Drosophila, and tobacco hornworm) belong to the c-type family. The large deviations in slope (about 2) of CH-type lysozymes as seen in Figure 1 are suggestive of explicit difference in their molecular structures from those of other lysozyme types.

Bottom Line: Hydrogen bonding was used as the side-chain property for searching the binding sites of lysozymes.Pattern similarity and average index values of structure-related properties of side chains in short segments of three residues or longer were, for the first time, successfully applied for predicting functional sites in sequences.This new approach may be applicable to studying functional sites in un-annotated proteins, for which complete 3D structures are not yet available.

View Article: PubMed Central - HTML - PubMed

Affiliation: Food, Nutrition and Health, The University of British Columbia, 6650 Marine Drive, Vancouver, B.C., Canada. shuryo.nakai@ubc.ca

ABSTRACT

Background: Although it is generally agreed that topography is more conserved than sequences, proteins sharing the same fold can have different functions, while there are protein families with low sequence similarity. An alternative method for profile analysis of characteristic conserved positions of the motifs within the 3D structures may be needed for functional annotation of protein sequences. Using the approach of quantitative structure-activity relationships (QSAR), we have proposed a new algorithm for postulating functional mechanisms on the basis of pattern similarity and average of property values of side-chains in segments within sequences. This approach was used to search for functional sites of proteins belonging to the lysozyme and cystatin families.

Results: Hydrophobicity and beta-turn propensity of reference segments with 3-7 residues were used for the homology similarity search (HSS) for active sites. Hydrogen bonding was used as the side-chain property for searching the binding sites of lysozymes. The profiles of similarity constants and average values of these parameters as functions of their positions in the sequences could identify both active and substrate binding sites of the lysozyme of Streptomyces coelicolor, which has been reported as a new fold enzyme (Cellosyl). The same approach was successfully applied to cystatins, especially for postulating the mechanisms of amyloidosis of human cystatin C as well as human lysozyme.

Conclusion: Pattern similarity and average index values of structure-related properties of side chains in short segments of three residues or longer were, for the first time, successfully applied for predicting functional sites in sequences. This new approach may be applicable to studying functional sites in un-annotated proteins, for which complete 3D structures are not yet available.

Show MeSH
Related in: MedlinePlus