Polyphosphate: From Bugs to Brains


PolyP is an ancient and ubiquitous energy‐rich molecule that has been shown to have many cellular roles in biology, yet a new fundamental biological role(s) may still await discovery.

Keywords: actin; endopolyphosphatase; exopolyphosphatase; polyP kinase; VTC proteins

Figure 1.

PolyP polymer.

Figure 2.

Ribbon structures of homologues of enzymes involved in polyphosphate metabolism and structure of the catalytic domain of exopolyphosphatase. The fold of the catalytic domain of Ppx is predicted to be similar to the fold of the ASKHA phosphotransferases (represented by acetate kinase (purple; protein data base (PDB) ID–1G99) (a)). Determination of the backbone structure of the catalytic domain of Ppx (blue) (b) confirms the prediction (Alvarado et al., 2004). The polyP‐dependent glucokinases are predicted to possess folds similar to that of the carboxy‐terminal catalytic domain of human hexokinase (gold; PDB ID–1CZA), which is also an ASKHA phosphotransferase (c). ScPPX1is predicted to have a similar fold to that of the RecJ endonuclease (orange; PDB ID–1IR6) (d). Whereas, Ppk1 is a member of a family of proteins that includes a bacterial endonuclease (green; PDB ID‐‐1BYR) (e), Ppk2 is a P‐loop phosphotransferase most closely related to the thymidylate kinases (magenta; PDB ID–4TMK) (f). This prediction has recently been confirmed by the report on the determination of the structure of the E. coli Ppk (Zhu et al., ). The polyP/ATP‐dependent NAD kinases are members of the phosphofructokinase (red; PDB‐ID–1PFK) (g) superfamily.



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Lichko LP, Kulakovskaya TV and Kulaev IS (2003) Nuclear exopolyphosphatase of Saccharomyces cerevisiae is not encoded by the PPX1 gene encoding the major yeast exopolyphosphatase. FEMS Yeast Research 3: 113–117.

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Tanaka S, Lee SO and Hamaoka K (2003) Strictly polyphosphate‐dependent glucokinase in a polyphosphate‐accumulating bacterium, Microlunatus phosphovorus. Journal of Bacteriology 185: 5654–5656.

Wang L, Fraley CD, Faridi J, Kornberg A and Roth RA (2003) Inorganic polyphosphate stimulates mammalian TOR, a kinase involved in the proliferation of mammary cancer cells. Proceedings of the National Academy of Sciences of the USA 100: 11249–11254.

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Further Reading

Ault‐Riché D and Kornberg A (1999) Definitive enzymatic assays in polyphosphate analysis. Progress in Molecular and Subcellular Biology 23: 241–252.

Das S, Seebach D and Reusch RN (2002) Differential effects of temperature on E. coli and synthetic polyhydroxybutyrate/polyphosphate channels. Biochemistry 41: 5307–5312.

Ishige K, Zhang H and Kornberg A (2002) Polyphosphate kinase (PPK2), a potent, polyphosphate‐driven generator of GTP. Proceedings of the National Academy of Sciences of the USA 99, 16684–16688.

Kuroda A, Nomura K, Ohtomo R et al. (2001) Role of inorganic polyphosphate in promoting ribosomal protein degradation by the Lon protease in E coli. Science 293: 705–708.

Kulaev IS, Kulakovskaya TV, Andreeva NA and Lichko LP (1999) Metabolism and function of polyphosphates in bacteria and yeast. Progress in Molecular and Subcellular Biology 23: 27–43.

Leipe DD, Koonin EV and Aravind L (2003) Evolution and classification of P‐loop kinases and related proteins. Journal of Molecular Biology 333: 781–815.

Ogawa N, DeRisi J and Brown PO (2000) New components of a system for phosphate accumulation and polyphosphate metabolism in Saccharomyces cerevisiae revealed by genomic expression analysis. Molecular Biology of the Cell 11: 4309–4321.

Phillips NF, Hsieh PC and Kowalczyk TH (1999) Polyphosphate glucokinase. Progress in Molecular and Subcellular Biology 23: 101–125.

Rashid MH, Rumbaugh K, Passador L et al. (2000) Polyphosphate kinase is essential for biofilm development, quorum sensing, and virulence of Pseudomonas aeruginosa. Proceedings of the National Academy of Sciences of the USA 97: 9636–9641.

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Sanders, David A, and Wanner, Barry L(Jan 2006) Polyphosphate: From Bugs to Brains. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1038/npg.els.0000571]