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. 1997 Aug;6(8):1764–1767. doi: 10.1002/pro.5560060817

An unexpected structural relationship between integral membrane phosphatases and soluble haloperoxidases.

A F Neuwald 1
PMCID: PMC2143768  PMID: 9260289

Abstract

The mechanism of a membrane-bound enzyme important in phospholipid signaling, type 2 phosphatidic acid phosphatase, is suggested by sequence motifs shared with a soluble vanadium-dependent chloroperoxidase of known structure. These regions are also conserved in other soluble globular and membrane-associated proteins, including bacterial acid phosphatases, mammalian glucose-6-phosphatases, and the Drosophila developmental protein Wunen. This implies that a similar arrangement of catalytic residues specifies the active site within both soluble and membrane spanning domains.

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Selected References

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  1. Barilà D., Plateroti M., Nobili F., Muda A. O., Xie Y., Morimoto T., Perozzi G. The Dri 42 gene, whose expression is up-regulated during epithelial differentiation, encodes a novel endoplasmic reticulum resident transmembrane protein. J Biol Chem. 1996 Nov 22;271(47):29928–29936. doi: 10.1074/jbc.271.47.29928. [DOI] [PubMed] [Google Scholar]
  2. Denu J. M., Lohse D. L., Vijayalakshmi J., Saper M. A., Dixon J. E. Visualization of intermediate and transition-state structures in protein-tyrosine phosphatase catalysis. Proc Natl Acad Sci U S A. 1996 Mar 19;93(6):2493–2498. doi: 10.1073/pnas.93.6.2493. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Dillon D. A., Wu W. I., Riedel B., Wissing J. B., Dowhan W., Carman G. M. The Escherichia coli pgpB gene encodes for a diacylglycerol pyrophosphate phosphatase activity. J Biol Chem. 1996 Nov 29;271(48):30548–30553. doi: 10.1074/jbc.271.48.30548. [DOI] [PubMed] [Google Scholar]
  4. English D., Cui Y., Siddiqui R. A. Messenger functions of phosphatidic acid. Chem Phys Lipids. 1996 May 24;80(1-2):117–132. doi: 10.1016/0009-3084(96)02549-2. [DOI] [PubMed] [Google Scholar]
  5. Exton J. H. Phosphatidylcholine breakdown and signal transduction. Biochim Biophys Acta. 1994 Apr 14;1212(1):26–42. doi: 10.1016/0005-2760(94)90186-4. [DOI] [PubMed] [Google Scholar]
  6. Flores I., Casaseca T., Martinez-A C., Kanoh H., Merida I. Phosphatidic acid generation through interleukin 2 (IL-2)-induced alpha-diacylglycerol kinase activation is an essential step in IL-2-mediated lymphocyte proliferation. J Biol Chem. 1996 Apr 26;271(17):10334–10340. doi: 10.1074/jbc.271.17.10334. [DOI] [PubMed] [Google Scholar]
  7. Hashida-Okado T., Ogawa A., Endo M., Yasumoto R., Takesako K., Kato I. AUR1, a novel gene conferring aureobasidin resistance on Saccharomyces cerevisiae: a study of defective morphologies in Aur1p-depleted cells. Mol Gen Genet. 1996 May 23;251(2):236–244. doi: 10.1007/BF02172923. [DOI] [PubMed] [Google Scholar]
  8. Kai M., Wada I., Imai S., Sakane F., Kanoh H. Identification and cDNA cloning of 35-kDa phosphatidic acid phosphatase (type 2) bound to plasma membranes. Polymerase chain reaction amplification of mouse H2O2-inducible hic53 clone yielded the cDNA encoding phosphatidic acid phosphatase. J Biol Chem. 1996 Aug 2;271(31):18931–18938. doi: 10.1074/jbc.271.31.18931. [DOI] [PubMed] [Google Scholar]
  9. Kanoh H., Kai M., Wada I. Molecular properties of enzymes involved in diacylglycerol and phosphatidate metabolism. J Lipid Mediat Cell Signal. 1996 Sep;14(1-3):245–250. doi: 10.1016/0929-7855(96)00532-9. [DOI] [PubMed] [Google Scholar]
  10. Karlin S., Altschul S. F. Applications and statistics for multiple high-scoring segments in molecular sequences. Proc Natl Acad Sci U S A. 1993 Jun 15;90(12):5873–5877. doi: 10.1073/pnas.90.12.5873. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Kocsis M. G., Weselake R. J. Phosphatidate phosphatases of mammals, yeast, and higher plants. Lipids. 1996 Aug;31(8):785–802. doi: 10.1007/BF02522974. [DOI] [PubMed] [Google Scholar]
  12. Messerschmidt A., Wever R. X-ray structure of a vanadium-containing enzyme: chloroperoxidase from the fungus Curvularia inaequalis. Proc Natl Acad Sci U S A. 1996 Jan 9;93(1):392–396. doi: 10.1073/pnas.93.1.392. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Moolenaar W. H., Jalink K., van Corven E. J. Lysophosphatidic acid: a bioactive phospholipid with growth factor-like properties. Rev Physiol Biochem Pharmacol. 1992;119:47–65. doi: 10.1007/3540551921_3. [DOI] [PubMed] [Google Scholar]
  14. Moolenaar W. H. Lysophosphatidic acid signalling. Curr Opin Cell Biol. 1995 Apr;7(2):203–210. doi: 10.1016/0955-0674(95)80029-8. [DOI] [PubMed] [Google Scholar]
  15. Moolenaar W. H. Lysophosphatidic acid, a multifunctional phospholipid messenger. J Biol Chem. 1995 Jun 2;270(22):12949–12952. doi: 10.1074/jbc.270.22.12949. [DOI] [PubMed] [Google Scholar]
  16. Neuwald A. F., Liu J. S., Lawrence C. E. Gibbs motif sampling: detection of bacterial outer membrane protein repeats. Protein Sci. 1995 Aug;4(8):1618–1632. doi: 10.1002/pro.5560040820. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Neuwald A. F., Liu J. S., Lipman D. J., Lawrence C. E. Extracting protein alignment models from the sequence database. Nucleic Acids Res. 1997 May 1;25(9):1665–1677. doi: 10.1093/nar/25.9.1665. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Ollis D. L., Cheah E., Cygler M., Dijkstra B., Frolow F., Franken S. M., Harel M., Remington S. J., Silman I., Schrag J. The alpha/beta hydrolase fold. Protein Eng. 1992 Apr;5(3):197–211. doi: 10.1093/protein/5.3.197. [DOI] [PubMed] [Google Scholar]
  19. Rost B., Casadio R., Fariselli P., Sander C. Transmembrane helices predicted at 95% accuracy. Protein Sci. 1995 Mar;4(3):521–533. doi: 10.1002/pro.5560040318. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Stankiewicz P. J., Tracey A. S., Crans D. C. Inhibition of phosphate-metabolizing enzymes by oxovanadium(V) complexes. Met Ions Biol Syst. 1995;31:287–324. [PubMed] [Google Scholar]
  21. Stukey J., Carman G. M. Identification of a novel phosphatase sequence motif. Protein Sci. 1997 Feb;6(2):469–472. doi: 10.1002/pro.5560060226. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Thaller M. C., Berlutti F., Schippa S., Lombardi G., Rossolini G. M. Characterization and sequence of PhoC, the principal phosphate-irrepressible acid phosphatase of Morganella morganii. Microbiology. 1994 Jun;140(Pt 6):1341–1350. doi: 10.1099/00221287-140-6-1341. [DOI] [PubMed] [Google Scholar]
  23. Tong L., Qian C., Massariol M. J., Bonneau P. R., Cordingley M. G., Lagacé L. A new serine-protease fold revealed by the crystal structure of human cytomegalovirus protease. Nature. 1996 Sep 19;383(6597):272–275. doi: 10.1038/383272a0. [DOI] [PubMed] [Google Scholar]
  24. Vilter H. Vanadium-dependent haloperoxidases. Met Ions Biol Syst. 1995;31:325–362. [PubMed] [Google Scholar]
  25. Waggoner D. W., Gómez-Muñoz A., Dewald J., Brindley D. N. Phosphatidate phosphohydrolase catalyzes the hydrolysis of ceramide 1-phosphate, lysophosphatidate, and sphingosine 1-phosphate. J Biol Chem. 1996 Jul 12;271(28):16506–16509. doi: 10.1074/jbc.271.28.16506. [DOI] [PubMed] [Google Scholar]
  26. Zhang N., Zhang J., Purcell K. J., Cheng Y., Howard K. The Drosophila protein Wunen repels migrating germ cells. Nature. 1997 Jan 2;385(6611):64–67. doi: 10.1038/385064a0. [DOI] [PubMed] [Google Scholar]

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