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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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Multiple sequence alignment of five lysozymes belonging to four families.
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Figure 2: Multiple sequence alignment of five lysozymes belonging to four families.

Mentions: The HSS computer program was applied to the sequence alignment patterns shown in Figure 2 using the active sites of hen lysozyme at positions 54–57(F34ESN) and 80–83(T51DYG) as the references. The position numbers in parenthesis are the positions in un-gapped sequences of individual lysozymes, while the immediately preceding numbers outside of parenthesis are the position numbers of the multiple sequence alignment (gapped) in Figure 2. Since the peptidoglycan-lysing activity is associated with glutamic 55(E35) and aspartic 81(D52) side-chains in the hen lysozyme [13], the segments flanking these residues in the sequences were the focus of pattern similarity search using the HSS.


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

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

Multiple sequence alignment of five lysozymes belonging to four families.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 2: Multiple sequence alignment of five lysozymes belonging to four families.
Mentions: The HSS computer program was applied to the sequence alignment patterns shown in Figure 2 using the active sites of hen lysozyme at positions 54–57(F34ESN) and 80–83(T51DYG) as the references. The position numbers in parenthesis are the positions in un-gapped sequences of individual lysozymes, while the immediately preceding numbers outside of parenthesis are the position numbers of the multiple sequence alignment (gapped) in Figure 2. Since the peptidoglycan-lysing activity is associated with glutamic 55(E35) and aspartic 81(D52) side-chains in the hen lysozyme [13], the segments flanking these residues in the sequences were the focus of pattern similarity search using the HSS.

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