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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
Comparison of propensities between adenine and guanine phosphates with cyclic variants. (a) cAMP versus cGMP (b) cAMP versus AMP (c) cGMP versus GMP
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Figure 5: Comparison of propensities between adenine and guanine phosphates with cyclic variants. (a) cAMP versus cGMP (b) cAMP versus AMP (c) cGMP versus GMP

Mentions: Figure 5(a) shows a comparison of propensities between cyclic monophosphates of adenine and guanine (cAMP and cGMP). Correlation coefficients between the propensities are also shown in Table 2. Despite a relatively small amount of data for cGMP, propensities values between the two cyclic ligands are very similar with a correlation coefficient (R = 0.72) higher than any pair of ligands in this study. In contrast the cyclic and noncyclic variants have relatively lower degree of correlation (R = 0.42 for adenine and 0.27 for guanine), as can be seen from parts (b) and (c) of Figure 5 also. Thus, it is quite clear that the cAMP and cGMP have close similarity in their residue-wise interactions, whereas despite having a similar nucleotide base, their non-cyclic versions are quite different. This highlights the crucial significance of the phosphate part of the ligand for interaction with ligands, as this part of the nucleotide distinguishes between the chemical natures of cyclic AMPs from non-cyclic ones.


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)

Comparison of propensities between adenine and guanine phosphates with cyclic variants. (a) cAMP versus cGMP (b) cAMP versus AMP (c) cGMP versus GMP
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 5: Comparison of propensities between adenine and guanine phosphates with cyclic variants. (a) cAMP versus cGMP (b) cAMP versus AMP (c) cGMP versus GMP
Mentions: Figure 5(a) shows a comparison of propensities between cyclic monophosphates of adenine and guanine (cAMP and cGMP). Correlation coefficients between the propensities are also shown in Table 2. Despite a relatively small amount of data for cGMP, propensities values between the two cyclic ligands are very similar with a correlation coefficient (R = 0.72) higher than any pair of ligands in this study. In contrast the cyclic and noncyclic variants have relatively lower degree of correlation (R = 0.42 for adenine and 0.27 for guanine), as can be seen from parts (b) and (c) of Figure 5 also. Thus, it is quite clear that the cAMP and cGMP have close similarity in their residue-wise interactions, whereas despite having a similar nucleotide base, their non-cyclic versions are quite different. This highlights the crucial significance of the phosphate part of the ligand for interaction with ligands, as this part of the nucleotide distinguishes between the chemical natures of cyclic AMPs from non-cyclic ones.

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