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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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HSS search patterns for active sites in Strep. coelicolor lysozyme. Segment 79–83 (STDYG) of hen lysozyme was used as the reference based on charge.
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Figure 4: HSS search patterns for active sites in Strep. coelicolor lysozyme. Segment 79–83 (STDYG) of hen lysozyme was used as the reference based on charge.

Mentions: The same search was conducted for goose and T4 lysozymes as well as the new fold CH-lysozyme [12], with the assumption that it is an un-annotated sequence, to confirm validation of the HSS approach (Table 1). Two positions of 79(E73) and 103(D97) were determined as the active sites of the goose lysozyme sequence. D97 may not be essential for the catalytic activity of the goose lysozyme [15]. In comparison, 11(E11) and 20(D20) were noted for T4 lysozyme, which are in good agreement with those reported in the literature [13]. As shown in Figure 4, in the case of the sequence of Cellosyl (CH-type), 14(D9), 104(D98) and 106(E100) were identified as candidates to be the active positions of catalysis, which are in good agreement with Rau et al. [12]. These results would support the reliability of the HSS approach.


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

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

HSS search patterns for active sites in Strep. coelicolor lysozyme. Segment 79–83 (STDYG) of hen lysozyme was used as the reference based on charge.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 4: HSS search patterns for active sites in Strep. coelicolor lysozyme. Segment 79–83 (STDYG) of hen lysozyme was used as the reference based on charge.
Mentions: The same search was conducted for goose and T4 lysozymes as well as the new fold CH-lysozyme [12], with the assumption that it is an un-annotated sequence, to confirm validation of the HSS approach (Table 1). Two positions of 79(E73) and 103(D97) were determined as the active sites of the goose lysozyme sequence. D97 may not be essential for the catalytic activity of the goose lysozyme [15]. In comparison, 11(E11) and 20(D20) were noted for T4 lysozyme, which are in good agreement with those reported in the literature [13]. As shown in Figure 4, in the case of the sequence of Cellosyl (CH-type), 14(D9), 104(D98) and 106(E100) were identified as candidates to be the active positions of catalysis, which are in good agreement with Rau et al. [12]. These results would support the reliability of the HSS approach.

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