Converting a Kinase into a Phosphatase?

Science's STKE  14 Jan 2003:
Vol. 2003, Issue 165, pp. tw28-TW28
DOI: 10.1126/stke.2003.165.tw28

Bacillus subtilis respond to changes in carbon source by altering gene expression in a process called the carbon catabolite repression and carbon catabolite activation response (CCR/CCA). HPr is the histidine-containing protein, and HPr kinase/phosphatase (HPrK/P) is an enzyme that mediates CCR /CCA. Under conditions of high glucose HPrK/P acts as a kinase and phosphorylates HPr and catabolite repression HPr (CrH). Under starvation conditions, HPrK/P acts as a phosphatase, dephosphorylating CrH and HPr. The phosphorylated forms of HPr and CrH interact with the transcriptional regulator carbon catabolite control protein (CcpA). Ramström et al. used electrospray ionization mass spectroscopy to analyze the oligomeric state of the protein and determined that at pH 6.8, the enzyme was a hexamer, whereas at pH 9.5, the enzyme was mostly trimeric or dimeric. The kinase activity of the enzyme predominated at higher pH values, and the phosphatase activity predominated at lower pH values. During starvation conditions, the pH of the bacteria drops from 7.5 to 8 to about 6. Thus, a pH-driven change in oligomeric structure of HPrK/P may contribute to difference in enzymatic activity. HPrK/P is also regulated by allosteric modulators, such as inorganic phosphate, and glycolytic intermediates, such as fructose 1,6-diphosphate. Inorganic phosphate stimulated the phosphatase activity of the enzyme and fructose 1,6-diphosphate stimulated the kinase activity. Thus, through allosteric modulation and regulation of the oligomeric state in response to changes in pH, the HPrK/P can serve as either a kinase or a phosphatase to allow the bacteria to properly respond to changes in metabolic state.

H. Ramström, S. Sanlier, E. Leize-Wagner, C. Philippe, A. Van Dorsselaer, J. Haiech, Properties and regulation of the bifunctional enzyme HPr kinase/phosphatase in Bacillus subtilis. J. Biol. Chem. 278, 1174-1185 (2003). [Abstract] [Full Text]