A new family of phosphotransferases related to P-type ATPases

Abstract

We read with great interest the recent paper in TiBS by Aravind and colleagues[1xAravind, L., Galperin, M.Y., and Koonin, E.V. Trends Biochem. Sci. 1998; 23: 127–129Abstract | Full Text | Full Text PDF | PubMed | Scopus (223)See all References[1], in which the authors show that P-type ATPases belong to a large superfamily of enzymes that contains, among others, haloacid dehalogenase, phosphomannomutase and phosphoserine phosphatase. P-type ATPases share three motifs with these enzymes. The authors noticed that the first of these motifs (motif I) contains a conserved aspartate residue that has been shown to bind covalently to the phosphate group in P-type ATPases[2xPost, R.L. and Kume, S. J. Biol. Chem. 1973; 248: 6993–7000PubMedSee all References[2]and to an α-hydroxy acid in haloacid dehalogenases[3xLiu, J.Q. et al. J. Biol. Chem. 1995; 270: 18309–18312Crossref | PubMedSee all References[3].Our experimental data entirely support this view. We have recently shown that, when incubated with mannose 1,6-bisphosphate, phosphomannomutase becomes phosphorylated[4xPirard, M., Collet, J.F., Matthijs, G., and Van Schaftingen, E. FEBS Lett. 1997; 411: 251–254Abstract | Full Text | Full Text PDF | PubMed | Scopus (27)See all References[4]on the first aspartate residue of a conserved DXDXT/V motif that is found in several phosphomonoesterases and phosphomutases[5xCollet, J-F. et al. J. Biol. Chem. 1998; 273: 14107–14112Crossref | PubMed | Scopus (194)See all References[5]. This motif aligns with motif I described by Aravind and coauthors[1xAravind, L., Galperin, M.Y., and Koonin, E.V. Trends Biochem. Sci. 1998; 23: 127–129Abstract | Full Text | Full Text PDF | PubMed | Scopus (223)See all References[1]. Furthermore, phosphoserine phosphatase and β-phosphoglucomutase (not mentioned by Aravind et al.[1xAravind, L., Galperin, M.Y., and Koonin, E.V. Trends Biochem. Sci. 1998; 23: 127–129Abstract | Full Text | Full Text PDF | PubMed | Scopus (223)See all References[1]), which belong to the same family, form a phosphoenzyme that has the chemical characteristics of an acyl phosphate[5xCollet, J-F. et al. J. Biol. Chem. 1998; 273: 14107–14112Crossref | PubMed | Scopus (194)See all References, 6xCollet, J-F. et al. FEBS Lett. 1997; 408: 281–284Abstract | Full Text | Full Text PDF | PubMed | Scopus (43)See all References]. Finally, site-directed mutagenesis studies[5xCollet, J-F. et al. J. Biol. Chem. 1998; 273: 14107–14112Crossref | PubMed | Scopus (194)See all References[5], as well as more-direct chemical analysis (J-F. Collet, E. Van Schaftingen and Vincent Stroobant, unpublished), indicate that, at least for phosphoserine phosphatase, it is again the first aspartate of the DXDXT/V motif that is phosphorylated. These experimental findings, which are supported by sequence comparisons, led us to conclude that P-type ATPases and the enzymes mentioned by Aravind et al.[1xAravind, L., Galperin, M.Y., and Koonin, E.V. Trends Biochem. Sci. 1998; 23: 127–129Abstract | Full Text | Full Text PDF | PubMed | Scopus (223)See all References[1]share functional homology[5xCollet, J-F. et al. J. Biol. Chem. 1998; 273: 14107–14112Crossref | PubMed | Scopus (194)See all References, 6xCollet, J-F. et al. FEBS Lett. 1997; 408: 281–284Abstract | Full Text | Full Text PDF | PubMed | Scopus (43)See all References].