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Residue propensities, discrimination and binding site prediction of adenine and guanine phosphates.

Firoz A, Malik A, Joplin KH, Ahmad Z, Jha V, Ahmad S - BMC Biochem. (2011)

Bottom Line: This is likely to miss those where a similar binding site has not been previously characterized and when the binding sites do not follow the rule described by predefined motif.Results indicate that subtle differences exist between single residue preferences for specific nucleotides and taking neighbor environment and evolutionary context into account, successful models of their binding site prediction can be developed.This is expected to be helpful in identifying novel binding sites for adenine and guanine phosphates, especially when a known binding motif is not detectable.

View Article: PubMed Central - HTML - PubMed

Affiliation: Biomedical Informatics Center, PGIMER, Chandigarh-160012, India. adeel@netasa.org

ABSTRACT

Background: Adenine and guanine phosphates are involved in a number of biological processes such as cell signaling, metabolism and enzymatic cofactor functions. Binding sites in proteins for these ligands are often detected by looking for a previously known motif by alignment based search. This is likely to miss those where a similar binding site has not been previously characterized and when the binding sites do not follow the rule described by predefined motif. Also, it is intriguing how proteins select between adenine and guanine derivative with high specificity.

Results: Residue preferences for AMP, GMP, ADP, GDP, ATP and GTP have been investigated in details with additional comparison with cyclic variants cAMP and cGMP. We also attempt to predict residues interacting with these nucleotides using information derived from local sequence and evolutionary profiles. Results indicate that subtle differences exist between single residue preferences for specific nucleotides and taking neighbor environment and evolutionary context into account, successful models of their binding site prediction can be developed.

Conclusion: In this work, we explore how single amino acid propensities for these nucleotides play a role in the affinity and specificity of this set of nucleotides. This is expected to be helpful in identifying novel binding sites for adenine and guanine phosphates, especially when a known binding motif is not detectable.

Show MeSH
Amino acid propensities for various adenine phosphates (a) any contact between protein and nucleotide (b) protein main-chain contact with nucleotide base (c) protein main-chain contact with phosphate (d) protein side-chain contact with nucleotide base (e) protein side-chain contact with phosphate
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Figure 2: Amino acid propensities for various adenine phosphates (a) any contact between protein and nucleotide (b) protein main-chain contact with nucleotide base (c) protein main-chain contact with phosphate (d) protein side-chain contact with nucleotide base (e) protein side-chain contact with phosphate

Mentions: Figure 2 shows residue propensities in mono-, di- and tri- nucleotides of adenine both in the overall (Figure 2(a)) as well as higher resolution contact definitions (Figure 2(b-e)). A number of observations can be made from these graphs.


Residue propensities, discrimination and binding site prediction of adenine and guanine phosphates.

Firoz A, Malik A, Joplin KH, Ahmad Z, Jha V, Ahmad S - BMC Biochem. (2011)

Amino acid propensities for various adenine phosphates (a) any contact between protein and nucleotide (b) protein main-chain contact with nucleotide base (c) protein main-chain contact with phosphate (d) protein side-chain contact with nucleotide base (e) protein side-chain contact with phosphate
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3113737&req=5

Figure 2: Amino acid propensities for various adenine phosphates (a) any contact between protein and nucleotide (b) protein main-chain contact with nucleotide base (c) protein main-chain contact with phosphate (d) protein side-chain contact with nucleotide base (e) protein side-chain contact with phosphate
Mentions: Figure 2 shows residue propensities in mono-, di- and tri- nucleotides of adenine both in the overall (Figure 2(a)) as well as higher resolution contact definitions (Figure 2(b-e)). A number of observations can be made from these graphs.

Bottom Line: This is likely to miss those where a similar binding site has not been previously characterized and when the binding sites do not follow the rule described by predefined motif.Results indicate that subtle differences exist between single residue preferences for specific nucleotides and taking neighbor environment and evolutionary context into account, successful models of their binding site prediction can be developed.This is expected to be helpful in identifying novel binding sites for adenine and guanine phosphates, especially when a known binding motif is not detectable.

View Article: PubMed Central - HTML - PubMed

Affiliation: Biomedical Informatics Center, PGIMER, Chandigarh-160012, India. adeel@netasa.org

ABSTRACT

Background: Adenine and guanine phosphates are involved in a number of biological processes such as cell signaling, metabolism and enzymatic cofactor functions. Binding sites in proteins for these ligands are often detected by looking for a previously known motif by alignment based search. This is likely to miss those where a similar binding site has not been previously characterized and when the binding sites do not follow the rule described by predefined motif. Also, it is intriguing how proteins select between adenine and guanine derivative with high specificity.

Results: Residue preferences for AMP, GMP, ADP, GDP, ATP and GTP have been investigated in details with additional comparison with cyclic variants cAMP and cGMP. We also attempt to predict residues interacting with these nucleotides using information derived from local sequence and evolutionary profiles. Results indicate that subtle differences exist between single residue preferences for specific nucleotides and taking neighbor environment and evolutionary context into account, successful models of their binding site prediction can be developed.

Conclusion: In this work, we explore how single amino acid propensities for these nucleotides play a role in the affinity and specificity of this set of nucleotides. This is expected to be helpful in identifying novel binding sites for adenine and guanine phosphates, especially when a known binding motif is not detectable.

Show MeSH