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Phosphate binding sites identification in protein structures.

Parca L, Gherardini PF, Helmer-Citterich M, Ausiello G - Nucleic Acids Res. (2010)

Bottom Line: Pfinder has been tested on a data set of 52 proteins for which both the apo and holo forms were available.We obtained at least one correct prediction in 63% of the holo structures and in 62% of the apo.The ability of Pfinder to recognize a phosphate-binding site in unbound protein structures makes it an ideal tool for functional annotation and for complementing docking and drug design methods.

View Article: PubMed Central - PubMed

Affiliation: Department of Biology, Centre for Molecular Bioinformatics, University of Rome Tor Vergata, Via della Ricerca Scientifica snc, 00133 Rome, Italy.

ABSTRACT
Nearly half of known protein structures interact with phosphate-containing ligands, such as nucleotides and other cofactors. Many methods have been developed for the identification of metal ions-binding sites and some for bigger ligands such as carbohydrates, but none is yet available for the prediction of phosphate-binding sites. Here we describe Pfinder, a method that predicts binding sites for phosphate groups, both in the form of ions or as parts of other non-peptide ligands, in proteins of known structure. Pfinder uses the Query3D local structural comparison algorithm to scan a protein structure for the presence of a number of structural motifs identified for their ability to bind the phosphate chemical group. Pfinder has been tested on a data set of 52 proteins for which both the apo and holo forms were available. We obtained at least one correct prediction in 63% of the holo structures and in 62% of the apo. The ability of Pfinder to recognize a phosphate-binding site in unbound protein structures makes it an ideal tool for functional annotation and for complementing docking and drug design methods. The Pfinder program is available at http://pdbfun.uniroma2.it/pfinder.

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Two examples of PbMs used by the method. Each motif is represented by the residues forming the motif, that belong to different structures, and their corresponding bound ligands. Carbon atoms of the binding residues are in purple while those belonging to the ligand are in white, all the other atoms are colored by type (phosphorus in orange, oxygen in red, nitrogen in light blue, sulphur in yellow). (A) PbM (id 598). The motif is [V,M]-G-[N,A,S]-S where the final serine residue is present in only two of the three protein structures with different folds that share the motif. The three structures belong to a inositol-1′-phosphate synthase from M. tubercolosis (PDB code 1GR0), to an adenylyltransferase from Methanobacterium thermoautotrophicum (PDB code 1M8F) and to the Klebsiella pneumoniae acetolactate synthase (PDB code 1OZH). (B) PbM (id 1075). Two glycines and an alanine interact with the phosphate groups forming a G-A-G motif in two protein structures with different folds. The two structures belong to a Thermus thermophilus kinase (PDB code 1V1B) and to a histone acetyltransferase from Saccharomyces cerevisiae (PDB code 1QSM).
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Figure 1: Two examples of PbMs used by the method. Each motif is represented by the residues forming the motif, that belong to different structures, and their corresponding bound ligands. Carbon atoms of the binding residues are in purple while those belonging to the ligand are in white, all the other atoms are colored by type (phosphorus in orange, oxygen in red, nitrogen in light blue, sulphur in yellow). (A) PbM (id 598). The motif is [V,M]-G-[N,A,S]-S where the final serine residue is present in only two of the three protein structures with different folds that share the motif. The three structures belong to a inositol-1′-phosphate synthase from M. tubercolosis (PDB code 1GR0), to an adenylyltransferase from Methanobacterium thermoautotrophicum (PDB code 1M8F) and to the Klebsiella pneumoniae acetolactate synthase (PDB code 1OZH). (B) PbM (id 1075). Two glycines and an alanine interact with the phosphate groups forming a G-A-G motif in two protein structures with different folds. The two structures belong to a Thermus thermophilus kinase (PDB code 1V1B) and to a histone acetyltransferase from Saccharomyces cerevisiae (PDB code 1QSM).

Mentions: Pfinder uses a previously defined set of PbMs (18). In that study a number of structural motifs shared by at least two folds and associated with specific ligand fragments were identified. From that data set we selected only the motifs interacting with a phosphate group. Our final data set therefore contains 231 motifs, composed by at least three residues, that are present in at least two different SCOP (24) folds and bind at least one phosphate group. Since each motif is represented by a different protein structure for each different fold in which the motif is present we selected a representative structure to be used as reference (Figure 1). In choosing the representative structure for each motif we adhered to the following criteria:


Phosphate binding sites identification in protein structures.

Parca L, Gherardini PF, Helmer-Citterich M, Ausiello G - Nucleic Acids Res. (2010)

Two examples of PbMs used by the method. Each motif is represented by the residues forming the motif, that belong to different structures, and their corresponding bound ligands. Carbon atoms of the binding residues are in purple while those belonging to the ligand are in white, all the other atoms are colored by type (phosphorus in orange, oxygen in red, nitrogen in light blue, sulphur in yellow). (A) PbM (id 598). The motif is [V,M]-G-[N,A,S]-S where the final serine residue is present in only two of the three protein structures with different folds that share the motif. The three structures belong to a inositol-1′-phosphate synthase from M. tubercolosis (PDB code 1GR0), to an adenylyltransferase from Methanobacterium thermoautotrophicum (PDB code 1M8F) and to the Klebsiella pneumoniae acetolactate synthase (PDB code 1OZH). (B) PbM (id 1075). Two glycines and an alanine interact with the phosphate groups forming a G-A-G motif in two protein structures with different folds. The two structures belong to a Thermus thermophilus kinase (PDB code 1V1B) and to a histone acetyltransferase from Saccharomyces cerevisiae (PDB code 1QSM).
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3045618&req=5

Figure 1: Two examples of PbMs used by the method. Each motif is represented by the residues forming the motif, that belong to different structures, and their corresponding bound ligands. Carbon atoms of the binding residues are in purple while those belonging to the ligand are in white, all the other atoms are colored by type (phosphorus in orange, oxygen in red, nitrogen in light blue, sulphur in yellow). (A) PbM (id 598). The motif is [V,M]-G-[N,A,S]-S where the final serine residue is present in only two of the three protein structures with different folds that share the motif. The three structures belong to a inositol-1′-phosphate synthase from M. tubercolosis (PDB code 1GR0), to an adenylyltransferase from Methanobacterium thermoautotrophicum (PDB code 1M8F) and to the Klebsiella pneumoniae acetolactate synthase (PDB code 1OZH). (B) PbM (id 1075). Two glycines and an alanine interact with the phosphate groups forming a G-A-G motif in two protein structures with different folds. The two structures belong to a Thermus thermophilus kinase (PDB code 1V1B) and to a histone acetyltransferase from Saccharomyces cerevisiae (PDB code 1QSM).
Mentions: Pfinder uses a previously defined set of PbMs (18). In that study a number of structural motifs shared by at least two folds and associated with specific ligand fragments were identified. From that data set we selected only the motifs interacting with a phosphate group. Our final data set therefore contains 231 motifs, composed by at least three residues, that are present in at least two different SCOP (24) folds and bind at least one phosphate group. Since each motif is represented by a different protein structure for each different fold in which the motif is present we selected a representative structure to be used as reference (Figure 1). In choosing the representative structure for each motif we adhered to the following criteria:

Bottom Line: Pfinder has been tested on a data set of 52 proteins for which both the apo and holo forms were available.We obtained at least one correct prediction in 63% of the holo structures and in 62% of the apo.The ability of Pfinder to recognize a phosphate-binding site in unbound protein structures makes it an ideal tool for functional annotation and for complementing docking and drug design methods.

View Article: PubMed Central - PubMed

Affiliation: Department of Biology, Centre for Molecular Bioinformatics, University of Rome Tor Vergata, Via della Ricerca Scientifica snc, 00133 Rome, Italy.

ABSTRACT
Nearly half of known protein structures interact with phosphate-containing ligands, such as nucleotides and other cofactors. Many methods have been developed for the identification of metal ions-binding sites and some for bigger ligands such as carbohydrates, but none is yet available for the prediction of phosphate-binding sites. Here we describe Pfinder, a method that predicts binding sites for phosphate groups, both in the form of ions or as parts of other non-peptide ligands, in proteins of known structure. Pfinder uses the Query3D local structural comparison algorithm to scan a protein structure for the presence of a number of structural motifs identified for their ability to bind the phosphate chemical group. Pfinder has been tested on a data set of 52 proteins for which both the apo and holo forms were available. We obtained at least one correct prediction in 63% of the holo structures and in 62% of the apo. The ability of Pfinder to recognize a phosphate-binding site in unbound protein structures makes it an ideal tool for functional annotation and for complementing docking and drug design methods. The Pfinder program is available at http://pdbfun.uniroma2.it/pfinder.

Show MeSH
Related in: MedlinePlus