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. 1998 Aug;7(8):1829–1835. doi: 10.1002/pro.5560070819

A superfamily of metalloenzymes unifies phosphopentomutase and cofactor-independent phosphoglycerate mutase with alkaline phosphatases and sulfatases.

M Y Galperin 1, A Bairoch 1, E V Koonin 1
PMCID: PMC2144072  PMID: 10082381

Abstract

Sequence analysis of the probable archaeal phosphoglycerate mutase resulted in the identification of a superfamily of metalloenzymes with similar metal-binding sites and predicted conserved structural fold. This superfamily unites alkaline phosphatase, N-acetylgalactosamine-4-sulfatase, and cerebroside sulfatase, enzymes with known three-dimensional structures, with phosphopentomutase, 2,3-bisphosphoglycerate-independent phosphoglycerate mutase, phosphoglycerol transferase, phosphonate monoesterase, streptomycin-6-phosphate phosphatase, alkaline phosphodiesterase/nucleotide pyrophosphatase PC-1, and several closely related sulfatases. In addition to the metal-binding motifs, all these enzymes contain a set of conserved amino acid residues that are likely to be required for the enzymatic activity. Mutational changes in the vicinity of these residues in several sulfatases cause mucopolysaccharidosis (Hunter, Maroteaux-Lamy, Morquio, and Sanfilippo syndromes) and metachromatic leucodystrophy.

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Selected References

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  1. Alperin E. S., Shapiro L. J. Characterization of point mutations in patients with X-linked ichthyosis. Effects on the structure and function of the steroid sulfatase protein. J Biol Chem. 1997 Aug 15;272(33):20756–20763. doi: 10.1074/jbc.272.33.20756. [DOI] [PubMed] [Google Scholar]
  2. Belli S. I., Sali A., Goding J. W. Divalent cations stabilize the conformation of plasma cell membrane glycoprotein PC-1 (alkaline phosphodiesterase I). Biochem J. 1994 Nov 15;304(Pt 1):75–80. doi: 10.1042/bj3040075. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bielicki J., Freeman C., Clements P. R., Hopwood J. J. Human liver iduronate-2-sulphatase. Purification, characterization and catalytic properties. Biochem J. 1990 Oct 1;271(1):75–86. doi: 10.1042/bj2710075. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bielicki J., Hopwood J. J. Human liver N-acetylgalactosamine 6-sulphatase. Purification and characterization. Biochem J. 1991 Oct 15;279(Pt 2):515–520. doi: 10.1042/bj2790515. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Blättler W. A., Knowles J. R. Phosphoglycerate mutases: stereochemical course of the phosphoryl group transfers catalyzed by the cofactor-dependent enzyme from rabbit muscle and the cofactor-independent enzyme from wheat germ. Biochemistry. 1980 Feb 19;19(4):738–743. doi: 10.1021/bi00545a020. [DOI] [PubMed] [Google Scholar]
  6. Bond C. S., Clements P. R., Ashby S. J., Collyer C. A., Harrop S. J., Hopwood J. J., Guss J. M. Structure of a human lysosomal sulfatase. Structure. 1997 Feb 15;5(2):277–289. doi: 10.1016/s0969-2126(97)00185-8. [DOI] [PubMed] [Google Scholar]
  7. Botha F. C., Dennis D. T. Isozymes of phosphoglyceromutase from the developing endosperm of Ricinus communis: isolation and kinetic properties. Arch Biochem Biophys. 1986 Feb 15;245(1):96–103. doi: 10.1016/0003-9861(86)90193-1. [DOI] [PubMed] [Google Scholar]
  8. Breathnach R., Knowles J. R. Phosphoglycerate mutase from wheat germ: studies with 18O-labeled substrate, investigations of the phosphatase and phosphoryl transfer activities, and evidence for a phosphoryl-enzyme intermediate. Biochemistry. 1977 Jul 12;16(14):3054–3060. doi: 10.1021/bi00633a002. [DOI] [PubMed] [Google Scholar]
  9. Bult C. J., White O., Olsen G. J., Zhou L., Fleischmann R. D., Sutton G. G., Blake J. A., FitzGerald L. M., Clayton R. A., Gocayne J. D. Complete genome sequence of the methanogenic archaeon, Methanococcus jannaschii. Science. 1996 Aug 23;273(5278):1058–1073. doi: 10.1126/science.273.5278.1058. [DOI] [PubMed] [Google Scholar]
  10. Clair T., Lee H. Y., Liotta L. A., Stracke M. L. Autotaxin is an exoenzyme possessing 5'-nucleotide phosphodiesterase/ATP pyrophosphatase and ATPase activities. J Biol Chem. 1997 Jan 10;272(2):996–1001. doi: 10.1074/jbc.272.2.996. [DOI] [PubMed] [Google Scholar]
  11. Desrosiers M. G., Gately L. J., Gambel A. M., Menick D. R. Purification and characterization of the Ca2+-ATPase of Flavobacterium odoratum. J Biol Chem. 1996 Feb 16;271(7):3945–3951. doi: 10.1074/jbc.271.7.3945. [DOI] [PubMed] [Google Scholar]
  12. Dotson S. B., Smith C. E., Ling C. S., Barry G. F., Kishore G. M. Identification, characterization, and cloning of a phosphonate monoester hydrolase from Burkholderia caryophilli PG2982. J Biol Chem. 1996 Oct 18;271(42):25754–25761. doi: 10.1074/jbc.271.42.25754. [DOI] [PubMed] [Google Scholar]
  13. Fothergill-Gilmore L. A., Watson H. C. The phosphoglycerate mutases. Adv Enzymol Relat Areas Mol Biol. 1989;62:227–313. doi: 10.1002/9780470123089.ch6. [DOI] [PubMed] [Google Scholar]
  14. Freeman C., Hopwood J. J. Human glucosamine-6-sulphatase deficiency. Diagnostic enzymology towards heparin-derived trisaccharide substrates. Biochem J. 1992 Mar 1;282(Pt 2):605–614. doi: 10.1042/bj2820605. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Freeman C., Hopwood J. J. Human liver N-acetylglucosamine-6-sulphate sulphatase. Catalytic properties. Biochem J. 1987 Sep 1;246(2):355–365. doi: 10.1042/bj2460355. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Graña X., Pérez de la Ossa P., Broceño C., Stöcker M., Garriga J., Puigdomènech P., Climent F. 2,3-Bisphosphoglycerate-independent phosphoglycerate mutase is conserved among different phylogenic kingdoms. Comp Biochem Physiol B Biochem Mol Biol. 1995 Oct;112(2):287–293. doi: 10.1016/0305-0491(95)00076-3. [DOI] [PubMed] [Google Scholar]
  17. Graña X., de Lecea L., el-Maghrabi M. R., Ureña J. M., Caellas C., Carreras J., Puigdomenech P., Pilkis S. J., Climent F. Cloning and sequencing of a cDNA encoding 2,3-bisphosphoglycerate-independent phosphoglycerate mutase from maize. Possible relationship to the alkaline phosphatase family. J Biol Chem. 1992 Jun 25;267(18):12797–12803. [PubMed] [Google Scholar]
  18. Hammer-Jespersen K., Munch-Petersen A. Phosphodeoxyribomutase from Escherichia coli. Purification and some properties. Eur J Biochem. 1970 Dec;17(3):397–407. doi: 10.1111/j.1432-1033.1970.tb01179.x. [DOI] [PubMed] [Google Scholar]
  19. Henthorn P. S., Raducha M., Fedde K. N., Lafferty M. A., Whyte M. P. Different missense mutations at the tissue-nonspecific alkaline phosphatase gene locus in autosomal recessively inherited forms of mild and severe hypophosphatasia. Proc Natl Acad Sci U S A. 1992 Oct 15;89(20):9924–9928. doi: 10.1073/pnas.89.20.9924. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Huang Y., Blakeley S. D., McAleese S. M., Fothergill-Gilmore L. A., Dennis D. T. Higher-plant cofactor-independent phosphoglyceromutase: purification, molecular characterization and expression. Plant Mol Biol. 1993 Dec;23(5):1039–1053. doi: 10.1007/BF00021818. [DOI] [PubMed] [Google Scholar]
  21. Huang Y., Dennis D. T. Histidine residues 139, 363 and 500 are essential for catalytic activity of cofactor-independent phosphoglyceromutase from developing endosperm of the castor plant. Eur J Biochem. 1995 Apr 15;229(2):395–402. doi: 10.1111/j.1432-1033.1995.tb20480.x. [DOI] [PubMed] [Google Scholar]
  22. Jackson B. J., Kennedy E. P. The biosynthesis of membrane-derived oligosaccharides. A membrane-bound phosphoglycerol transferase. J Biol Chem. 1983 Feb 25;258(4):2394–2398. [PubMed] [Google Scholar]
  23. Kahn D. W., Anderson B. M. Characterization of Haemophilus influenzae nucleotide pyrophosphatase. An enzyme of critical importance for growth of the organism. J Biol Chem. 1986 May 5;261(13):6016–6025. [PubMed] [Google Scholar]
  24. Kim E. E., Wyckoff H. W. Reaction mechanism of alkaline phosphatase based on crystal structures. Two-metal ion catalysis. J Mol Biol. 1991 Mar 20;218(2):449–464. doi: 10.1016/0022-2836(91)90724-k. [DOI] [PubMed] [Google Scholar]
  25. Klenk H. P., Clayton R. A., Tomb J. F., White O., Nelson K. E., Ketchum K. A., Dodson R. J., Gwinn M., Hickey E. K., Peterson J. D. The complete genome sequence of the hyperthermophilic, sulphate-reducing archaeon Archaeoglobus fulgidus. Nature. 1997 Nov 27;390(6658):364–370. doi: 10.1038/37052. [DOI] [PubMed] [Google Scholar]
  26. Koonin E. V., Mushegian A. R., Galperin M. Y., Walker D. R. Comparison of archaeal and bacterial genomes: computer analysis of protein sequences predicts novel functions and suggests a chimeric origin for the archaea. Mol Microbiol. 1997 Aug;25(4):619–637. doi: 10.1046/j.1365-2958.1997.4821861.x. [DOI] [PubMed] [Google Scholar]
  27. Kuhn N. J., Setlow B., Setlow P., Cammack R., Williams R. Cooperative manganese (II) activation of 3-phosphoglycerate mutase of Bacillus megaterium: a biological pH-sensing mechanism in bacterial spore formation and germination. Arch Biochem Biophys. 1995 Jun 20;320(1):35–42. doi: 10.1006/abbi.1995.1339. [DOI] [PubMed] [Google Scholar]
  28. Kuhn N. J., Setlow B., Setlow P. Manganese(II) activation of 3-phosphoglycerate mutase of Bacillus megaterium: pH-sensitive interconversion of active and inactive forms. Arch Biochem Biophys. 1993 Nov 1;306(2):342–349. doi: 10.1006/abbi.1993.1521. [DOI] [PubMed] [Google Scholar]
  29. Kulakova A. N., Kulakov L. A., Quinn J. P. Cloning of the phosphonoacetate hydrolase gene from Pseudomonas fluorescens 23F encoding a new type of carbon-phosphorus bond cleaving enzyme and its expression in Escherichia coli and Pseudomonas putida. Gene. 1997 Aug 11;195(1):49–53. doi: 10.1016/s0378-1119(97)00151-0. [DOI] [PubMed] [Google Scholar]
  30. Leadlay P. F., Breathnach R., Gatehouse J. A., Johnson P. E., Knowles J. R. Phosphoglycerate mutase from wheat germ: studies with isotopically labeled 3-phospho-D-glycerates showing that the catalyzed reaction is intramolecular. Appendix: phosphoglycerate mutase from wheat germ: isolation, crystallization, and properties. Biochemistry. 1977 Jul 12;16(14):3045–3053. doi: 10.1021/bi00633a001. [DOI] [PubMed] [Google Scholar]
  31. Lee N., Carbon J. Nucleotide sequence of the 5' end of araBAD operon messenger RNA in Escherichia coli B/r. Proc Natl Acad Sci U S A. 1977 Jan;74(1):49–53. doi: 10.1073/pnas.74.1.49. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Lissens W., Vervoort R., Van Regemorter N., Van Bogaert P., Freund M., Verellen-Dumoulin C., Seneca S., Liebaers I. A D255H substitution in the arylsulphatase A gene of two unrelated Belgian patients with late-infantile metachromatic leukodystrophy. J Inherit Metab Dis. 1996;19(6):782–786. doi: 10.1007/BF01799173. [DOI] [PubMed] [Google Scholar]
  33. Lukatela G., Krauss N., Theis K., Selmer T., Gieselmann V., von Figura K., Saenger W. Crystal structure of human arylsulfatase A: the aldehyde function and the metal ion at the active site suggest a novel mechanism for sulfate ester hydrolysis. Biochemistry. 1998 Mar 17;37(11):3654–3664. doi: 10.1021/bi9714924. [DOI] [PubMed] [Google Scholar]
  34. Maddux B. A., Sbraccia P., Kumakura S., Sasson S., Youngren J., Fisher A., Spencer S., Grupe A., Henzel W., Stewart T. A. Membrane glycoprotein PC-1 and insulin resistance in non-insulin-dependent diabetes mellitus. Nature. 1995 Feb 2;373(6513):448–451. doi: 10.1038/373448a0. [DOI] [PubMed] [Google Scholar]
  35. Mansouri K., Piepersberg W. Genetics of streptomycin production in Streptomyces griseus: nucleotide sequence of five genes, strFGHIK, including a phosphatase gene. Mol Gen Genet. 1991 Sep;228(3):459–469. doi: 10.1007/BF00260640. [DOI] [PubMed] [Google Scholar]
  36. McGrath J. W., Wisdom G. B., McMullan G., Larkin M. J., Quinn J. P. The purification and properties of phosphonoacetate hydrolase, a novel carbon-phosphorus bond-cleavage enzyme from Pseudomonas fluorescens 23F. Eur J Biochem. 1995 Nov 15;234(1):225–230. doi: 10.1111/j.1432-1033.1995.225_c.x. [DOI] [PubMed] [Google Scholar]
  37. Morris V. L., Jackson D. P., Grattan M., Ainsworth T., Cuppels D. A. Isolation and sequence analysis of the Pseudomonas syringae pv. tomato gene encoding a 2,3-diphosphoglycerate-independent phosphoglyceromutase. J Bacteriol. 1995 Apr;177(7):1727–1733. doi: 10.1128/jb.177.7.1727-1733.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Murphy J. E., Tibbitts T. T., Kantrowitz E. R. Mutations at positions 153 and 328 in Escherichia coli alkaline phosphatase provide insight towards the structure and function of mammalian and yeast alkaline phosphatases. J Mol Biol. 1995 Nov 3;253(4):604–617. doi: 10.1006/jmbi.1995.0576. [DOI] [PubMed] [Google Scholar]
  39. Nakashita H, Watanabe K, Hara O, Hidaka T, Seto H. Studies on the biosynthesis of bialaphos. Biochemical mechanism of C-P bond formation: discovery of phosphonopyruvate decarboxylase which catalyzes the formation of phosphonoacetaldehyde from phosphonopyruvate. J Antibiot (Tokyo) 1997 Mar;50(3):212–219. [PubMed] [Google Scholar]
  40. Oda Y., Kuo M. D., Huang S. S., Huang J. S. The major acidic fibroblast growth factor (aFGF)-stimulated phosphoprotein from bovine liver plasma membranes has aFGF-stimulated kinase, autoadenylylation, and alkaline nucleotide phosphodiesterase activities. J Biol Chem. 1993 Dec 25;268(36):27318–27326. [PubMed] [Google Scholar]
  41. Parenti G., Meroni G., Ballabio A. The sulfatase gene family. Curr Opin Genet Dev. 1997 Jun;7(3):386–391. doi: 10.1016/s0959-437x(97)80153-0. [DOI] [PubMed] [Google Scholar]
  42. Peiffer W. E., Desrosiers M. G., Menick D. R. Cloning and expression of the unique Ca2+-ATPase from Flavobacterium odoratum. J Biol Chem. 1996 Mar 1;271(9):5095–5100. doi: 10.1074/jbc.271.9.5095. [DOI] [PubMed] [Google Scholar]
  43. Singh R. P., Setlow P. Phosphoglycerate mutase in developing forespores of Bacillus megaterium may be regulated by the intrasporal level of free manganous ion. Biochem Biophys Res Commun. 1978 May 15;82(1):1–5. doi: 10.1016/0006-291x(78)90567-3. [DOI] [PubMed] [Google Scholar]
  44. Singh R. P., Setlow P. Purification and properties of phosphoglycerate phosphomutase from spores and cells of Bacillus megaterium. J Bacteriol. 1979 Feb;137(2):1024–1027. doi: 10.1128/jb.137.2.1024-1027.1979. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Smith D. R., Doucette-Stamm L. A., Deloughery C., Lee H., Dubois J., Aldredge T., Bashirzadeh R., Blakely D., Cook R., Gilbert K. Complete genome sequence of Methanobacterium thermoautotrophicum deltaH: functional analysis and comparative genomics. J Bacteriol. 1997 Nov;179(22):7135–7155. doi: 10.1128/jb.179.22.7135-7155.1997. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Smith G. C., Hass L. F. Wheat germ phosphoglycerate mutase: purification, polymorphism, and inhibition. Biochem Biophys Res Commun. 1985 Sep 16;131(2):743–749. doi: 10.1016/0006-291x(85)91301-4. [DOI] [PubMed] [Google Scholar]
  47. Smith G. C., McWilliams A. D., Hass L. F. Wheat germ phosphoglycerate mutase: evidence for a metalloenzyme. Biochem Biophys Res Commun. 1986 Apr 14;136(1):336–340. doi: 10.1016/0006-291x(86)90915-0. [DOI] [PubMed] [Google Scholar]
  48. Watabe K., Freese E. Purification and properties of the manganese-dependent phosphoglycerate mutase of Bacillus subtilis. J Bacteriol. 1979 Feb;137(2):773–778. doi: 10.1128/jb.137.2.773-778.1979. [DOI] [PMC free article] [PubMed] [Google Scholar]

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