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Positively-charged semi-tunnel is a structural and surface characteristic of polyphosphate-binding proteins: an in-silico study.

Wei ZZ, Vatcher G, Tin AH, Teng JL, Wang J, Cui QH, Chen JG, Yu AC - PLoS ONE (2015)

Bottom Line: We found that the PCSTs in varied proteins were folded in different secondary structure compositions.Utilizing the PCST identified in the β subunit of PPK3, we predicted the potential polyP-binding domain of PPK3.The discovery of this feature facilitates future searches for polyP-binding proteins and discovery of the mechanisms for polyP-binding activities.

View Article: PubMed Central - PubMed

Affiliation: Neuroscience Research Institute, Peking University; Department of Neurobiology, School of Basic Medical Sciences, Peking University; Key Laboratory for Neuroscience (Peking University), Ministry of Education; Key Laboratory for Neuroscience (Peking University), National Health and Family Planning Commission, Beijing 100191, China.

ABSTRACT
Phosphate is essential for all major life processes, especially energy metabolism and signal transduction. A linear phosphate polymer, polyphosphate (polyP), linked by high-energy phosphoanhydride bonds, can interact with various proteins, playing important roles as an energy source and regulatory factor. However, polyP-binding structures are largely unknown. Here we proposed a putative polyP binding site, a positively-charged semi-tunnel (PCST), identified by surface electrostatics analyses in polyP kinases (PPKs) and many other polyP-related proteins. We found that the PCSTs in varied proteins were folded in different secondary structure compositions. Molecular docking calculations revealed a significant value for binding affinity to polyP in PCST-containing proteins. Utilizing the PCST identified in the β subunit of PPK3, we predicted the potential polyP-binding domain of PPK3. The discovery of this feature facilitates future searches for polyP-binding proteins and discovery of the mechanisms for polyP-binding activities. This should greatly enhance the understanding of the many physiological functions of protein-bound polyP and the involvement of polyP and polyP-binding proteins in various human diseases.

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Related in: MedlinePlus

Predicted binding energies of polyP to PPK partial structural analogues with or without a Positively-Charged Semi-Tunnel.Each circle or square represented an estimated free energy of binding from the molecular docking calculations using Ap5 ligand and different PPK partial structural analogues.
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pone.0123713.g003: Predicted binding energies of polyP to PPK partial structural analogues with or without a Positively-Charged Semi-Tunnel.Each circle or square represented an estimated free energy of binding from the molecular docking calculations using Ap5 ligand and different PPK partial structural analogues.

Mentions: The estimated binding energies of Ap6A to 233 structure chains that shared partial structural similarities to PPKs identified by the Dali program (S1 Table) were analyzed. Of the 233 structure chains, 93 had minimum estimated free energies of lower than 100 kcal/mol (37 in the range of 10~100 kcal/mol, 40 from 1~10 kcal/mol, 5 from 0~1 kcal/mol and the strongest 11 were below 0 kcal/mol), while the other 140 had minimum estimated free energies of higher than 102 kcal/mol (39, 59 and 42 had 104, 103 and 100 kcal/mol, respectively). We divided these analogs into two groups, PCST-containing and non-PCST-containing. Analysis of the two groups of predictive minimum binding free energies identified in the PPK partial structural analogs (Fig 3) revealed that the binding energies of polyP to the PCST-containing protein group were significantly lower than those of the non-PCST-containing protein group (unpaired t-test, p<0.05). This statistical result supported the correlation between PCST and predictive polyP-binding energies.


Positively-charged semi-tunnel is a structural and surface characteristic of polyphosphate-binding proteins: an in-silico study.

Wei ZZ, Vatcher G, Tin AH, Teng JL, Wang J, Cui QH, Chen JG, Yu AC - PLoS ONE (2015)

Predicted binding energies of polyP to PPK partial structural analogues with or without a Positively-Charged Semi-Tunnel.Each circle or square represented an estimated free energy of binding from the molecular docking calculations using Ap5 ligand and different PPK partial structural analogues.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4400040&req=5

pone.0123713.g003: Predicted binding energies of polyP to PPK partial structural analogues with or without a Positively-Charged Semi-Tunnel.Each circle or square represented an estimated free energy of binding from the molecular docking calculations using Ap5 ligand and different PPK partial structural analogues.
Mentions: The estimated binding energies of Ap6A to 233 structure chains that shared partial structural similarities to PPKs identified by the Dali program (S1 Table) were analyzed. Of the 233 structure chains, 93 had minimum estimated free energies of lower than 100 kcal/mol (37 in the range of 10~100 kcal/mol, 40 from 1~10 kcal/mol, 5 from 0~1 kcal/mol and the strongest 11 were below 0 kcal/mol), while the other 140 had minimum estimated free energies of higher than 102 kcal/mol (39, 59 and 42 had 104, 103 and 100 kcal/mol, respectively). We divided these analogs into two groups, PCST-containing and non-PCST-containing. Analysis of the two groups of predictive minimum binding free energies identified in the PPK partial structural analogs (Fig 3) revealed that the binding energies of polyP to the PCST-containing protein group were significantly lower than those of the non-PCST-containing protein group (unpaired t-test, p<0.05). This statistical result supported the correlation between PCST and predictive polyP-binding energies.

Bottom Line: We found that the PCSTs in varied proteins were folded in different secondary structure compositions.Utilizing the PCST identified in the β subunit of PPK3, we predicted the potential polyP-binding domain of PPK3.The discovery of this feature facilitates future searches for polyP-binding proteins and discovery of the mechanisms for polyP-binding activities.

View Article: PubMed Central - PubMed

Affiliation: Neuroscience Research Institute, Peking University; Department of Neurobiology, School of Basic Medical Sciences, Peking University; Key Laboratory for Neuroscience (Peking University), Ministry of Education; Key Laboratory for Neuroscience (Peking University), National Health and Family Planning Commission, Beijing 100191, China.

ABSTRACT
Phosphate is essential for all major life processes, especially energy metabolism and signal transduction. A linear phosphate polymer, polyphosphate (polyP), linked by high-energy phosphoanhydride bonds, can interact with various proteins, playing important roles as an energy source and regulatory factor. However, polyP-binding structures are largely unknown. Here we proposed a putative polyP binding site, a positively-charged semi-tunnel (PCST), identified by surface electrostatics analyses in polyP kinases (PPKs) and many other polyP-related proteins. We found that the PCSTs in varied proteins were folded in different secondary structure compositions. Molecular docking calculations revealed a significant value for binding affinity to polyP in PCST-containing proteins. Utilizing the PCST identified in the β subunit of PPK3, we predicted the potential polyP-binding domain of PPK3. The discovery of this feature facilitates future searches for polyP-binding proteins and discovery of the mechanisms for polyP-binding activities. This should greatly enhance the understanding of the many physiological functions of protein-bound polyP and the involvement of polyP and polyP-binding proteins in various human diseases.

Show MeSH
Related in: MedlinePlus