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JBIC Journal of Biological Inorganic Chemistry

, Volume 13, Issue 8, pp 1205–1218 | Cite as

Metal ions in biological catalysis: from enzyme databases to general principles

  • Claudia Andreini
  • Ivano Bertini
  • Gabriele Cavallaro
  • Gemma L. Holliday
  • Janet M. Thornton
Original Paper

Abstract

We analysed the roles and distribution of metal ions in enzymatic catalysis using available public databases and our new resource Metal-MACiE (http://www.ebi.ac.uk/thornton-srv/databases/Metal_MACiE/home.html). In Metal-MACiE, a database of metal-based reaction mechanisms, 116 entries covering 21% of the metal-dependent enzymes and 70% of the types of enzyme-catalysed chemical transformations are annotated according to metal function. We used Metal-MACiE to assess the functions performed by metals in biological catalysis and the relative frequencies of different metals in different roles, which can be related to their individual chemical properties and availability in the environment. The overall picture emerging from the overview of Metal-MACiE is that redox-inert metal ions are used in enzymes to stabilize negative charges and to activate substrates by virtue of their Lewis acid properties, whereas redox-active metal ions can be used both as Lewis acids and as redox centres. Magnesium and zinc are by far the most common ions of the first type, while calcium is relatively less used. Magnesium, however, is most often bound to phosphate groups of substrates and interacts with the enzyme only transiently, whereas the other metals are stably bound to the enzyme. The most common metal of the second type is iron, which is prevalent in the catalysis of redox reactions, followed by manganese, cobalt, molybdenum, copper and nickel. The control of the reactivity of redox-active metal ions may involve their association with organic cofactors to form stable units. This occurs sometimes for iron and nickel, and quite often for cobalt and molybdenum.

Keywords

Metal Enzyme Metalloenzyme Database Catalysis 

Notes

Acknowledgments

This work was supported by Ministero Italiano dell’Università e della Ricerca (MIUR) through the FIRB project RBLA032ZM7, by the European Union through EU-NMR contract 026145 and by Ente Cassa di Risparmio di Firenze. G.L.H. is funded by Wellcome Trust grant 062347. We acknowledge support from the EMBL.

Supplementary material

775_2008_404_MOESM1_ESM.pdf (110 kb)
Supplementary material (PDF 109 kb).

References

  1. 1.
    Bertini I, Gray HB, Stiefel EI, Valentine JS (2006) Biological inorganic chemistry. University Science Books, SausalitoGoogle Scholar
  2. 2.
    Frausto da Silva JJR, Williams RJP (2001) The biological chemistry of the elements: the inorganic chemistry of life. Oxford University Press, New YorkGoogle Scholar
  3. 3.
    Bertini I, Sigel A, Sigel H (2001) Handbook on metalloproteins. Marcel Dekker, New YorkGoogle Scholar
  4. 4.
    Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE (2000) Nucleic Acids Res 28:235–242PubMedCrossRefGoogle Scholar
  5. 5.
    Rawlings ND, Morton FR, Barrett AJ (2006) Nucleic Acids Res 34:D270–D272PubMedCrossRefGoogle Scholar
  6. 6.
    Schomburg I, Chang A, Ebeling C, Gremse M, Heldt C, Huhn G, Schomburg D (2004) Nucleic Acids Res 32:D431–D433PubMedCrossRefGoogle Scholar
  7. 7.
    Holliday GL, Almonacid DE, Bartlett GJ, O’Boyle NM, Torrance JW, Murray-Rust P, Mitchell JB, Thornton JM (2007) Nucleic Acids Res 35:D515–D520PubMedCrossRefGoogle Scholar
  8. 8.
    Joyce AR, Palsson BO (2006) Nat Rev Mol Cell Biol 7:198–210PubMedCrossRefGoogle Scholar
  9. 9.
    Bertini I, Cavallaro G (2008) J Biol Inorg Chem 13:3–14PubMedCrossRefGoogle Scholar
  10. 10.
    Martin AC (2004) Bioinformatics 20:986–988PubMedCrossRefGoogle Scholar
  11. 11.
    Blom NS, Tetreault S, Coulombe R, Sygusch J (1996) Nat Struct Biol 3:856–862PubMedCrossRefGoogle Scholar
  12. 12.
    Blom N, Sygusch J (1997) Nat Struct Biol 4:36–39PubMedCrossRefGoogle Scholar
  13. 13.
    Resnick SM, Lee K, Gibson DT (1996) J Ind Microbiol Biot 17:438–457CrossRefGoogle Scholar
  14. 14.
    Kanehisa M, Goto S (2000) Nucleic Acids Res 28:27–30PubMedCrossRefGoogle Scholar
  15. 15.
    McDonald AG, Boyce S, Moss GP, Dixon HB, Tipton KF (2007) BMC Biochem 8:14PubMedCrossRefGoogle Scholar
  16. 16.
    Blaszczyk J, Shi G, Yan H, Ji X (2000) Structure 8:1049–1058PubMedCrossRefGoogle Scholar
  17. 17.
    Li Y, Blaszczyk J, Wu Y, Shi G, Ji X, Yan H (2005) Biochemistry 44:8590–8599PubMedCrossRefGoogle Scholar
  18. 18.
    Carpenter EP, Hawkins AR, Frost JW, Brown KA (1998) Nature 394:299–302PubMedCrossRefGoogle Scholar
  19. 19.
    Christianson DW, Fierke CA (1996) Acc Chem Res 29:331–339CrossRefGoogle Scholar
  20. 20.
    Stec B, Holtz KM, Kantrowitz ER (2000) J Mol Biol 299:1303–1311PubMedCrossRefGoogle Scholar
  21. 21.
    Zalatan JG, Catrina I, Mitchell R, Grzyska PK, O’Brien PJ, Herschlag D, Hengge AC (2007) J Am Chem Soc 129:9789–9798PubMedCrossRefGoogle Scholar
  22. 22.
    Lesburg CA, Zhai G, Cane DE, Christianson DW (1997) Science 277:1820–1824PubMedCrossRefGoogle Scholar
  23. 23.
    Essen LO, Perisic O, Katan M, Wu Y, Roberts MF, Williams RL (1997) Biochemistry 36:1704–1718PubMedCrossRefGoogle Scholar
  24. 24.
    Tainer JA, Getzoff ED, Richardson JS, Richardson DC (1983) Nature 306:284–287PubMedCrossRefGoogle Scholar
  25. 25.
    Hart JP, Balbirnie MM, Ogihara NL, Nersissian AM, Weiss MS, Valentine JS, Eisenberg D (1999) Biochemistry 38:2167–2178PubMedCrossRefGoogle Scholar
  26. 26.
    Scrutton NS, Basran J, Wilson EK, Chohan KK, Jang MH, Sutcliffe MJ, Hille R (1999) Biochem Soc Trans 27:196–201PubMedGoogle Scholar
  27. 27.
    Roach PL, Clifton IJ, Hensgens CM, Shibata N, Schofield CJ, Hajdu J, Baldwin JE (1997) Nature 387:827–830PubMedCrossRefGoogle Scholar
  28. 28.
    Fitzpatrick PF (1999) Annu Rev Biochem 68:355–381PubMedCrossRefGoogle Scholar
  29. 29.
    Goldblatt C, Lenton TM, Watson AJ (2006) Nature 443:683–686PubMedCrossRefGoogle Scholar
  30. 30.
    Luthi D, Gunzel D, McGuigan JA (1999) Exp Physiol 84:231–252PubMedCrossRefGoogle Scholar
  31. 31.
    Maguire ME, Cowan JA (2002) Biometals 15:203–210PubMedCrossRefGoogle Scholar
  32. 32.
    Linse S, Forsén S (1995) Adv Second Messenger Phosphoprotein Res 30:89–151PubMedGoogle Scholar
  33. 33.
    Carafoli E (2002) Proc Natl Acad Sci USA 99:1115–1122PubMedCrossRefGoogle Scholar
  34. 34.
    Jaiswal JK (2001) J Biosci 26:357–363PubMedCrossRefGoogle Scholar
  35. 35.
    Dreyer MK, Schulz GE (1996) J Mol Biol 259:458–466PubMedCrossRefGoogle Scholar
  36. 36.
    Vallee BL, Auld DS (1990) Proc Natl Acad Sci USA 87:220–224PubMedCrossRefGoogle Scholar
  37. 37.
    Hao B, Gong W, Rajagopalan PT, Zhou Y, Pei D, Chan MK (1999) Biochemistry 38:4712–4719PubMedCrossRefGoogle Scholar
  38. 38.
    Christianson DW, Lipscomb WN (1989) Acc Chem Res 22:62–69CrossRefGoogle Scholar
  39. 39.
    Matthews BW (1988) Acc Chem Res 21:333–340CrossRefGoogle Scholar
  40. 40.
    Bertini I, Calderone V, Fragai M, Luchinat C, Maletta M, Yeo KJ (2006) Angew Chem Int Ed 45:7952–7955CrossRefGoogle Scholar
  41. 41.
    Aubert SD, Li Y, Raushel FM (2004) Biochemistry 43:5707–5715PubMedCrossRefGoogle Scholar
  42. 42.
    Chen G, Edwards T, D’souza VM, Holz RC (1997) Biochemistry 36:4278–4286PubMedCrossRefGoogle Scholar
  43. 43.
    Martin SF, Hergenrother PJ (1999) Biochemistry 38:4403–4408PubMedCrossRefGoogle Scholar
  44. 44.
    Klabunde T, Strater N, Frohlich R, Witzel H, Krebs B (1996) J Mol Biol 259:737–748PubMedCrossRefGoogle Scholar
  45. 45.
    Benini S, Rypniewski WR, Wilson KS, Mangani S, Ciurli S (2004) J Am Chem Soc 126:3714–3715PubMedCrossRefGoogle Scholar
  46. 46.
    Silverman DN, Lindskog S (1988) Acc Chem Res 21:30–36CrossRefGoogle Scholar
  47. 47.
    Whittaker MM, Barynin VV, Antonyuk SV, Whittaker JW (1999) Biochemistry 38:9126–9136PubMedCrossRefGoogle Scholar
  48. 48.
    Pittman JK (2005) New Phytol 167:733–742PubMedCrossRefGoogle Scholar
  49. 49.
    Holm RH, Kennepohl P, Solomon EI (1996) Chem Rev 96:2239–2314PubMedCrossRefGoogle Scholar
  50. 50.
    Nam W (2007) Acc Chem Res 40:522–531PubMedCrossRefGoogle Scholar
  51. 51.
    Costas M, Mehn MP, Jensen MP, Que L Jr (2004) Chem Rev 104:939–986PubMedCrossRefGoogle Scholar
  52. 52.
    Kopp DA, Lippard SJ (2002) Curr Opin Chem Biol 6:568–576PubMedCrossRefGoogle Scholar
  53. 53.
    Kovaleva EG, Neibergall MB, Chakrabarty S, Lipscomb JD (2007) Acc Chem Res 40:475–483PubMedCrossRefGoogle Scholar
  54. 54.
    Lindqvist Y, Huang W, Schneider G, Shanklin J (1996) EMBO J 15:4081–4092PubMedGoogle Scholar
  55. 55.
    Mowat CG, Wehenkel A, Green AJ, Walkinshaw MD, Reid GA, Chapman SK (2004) Biochemistry 43:9519–9526PubMedCrossRefGoogle Scholar
  56. 56.
    Tsukihara T, Aoyama H, Yamashita E, Tomizaki T, Yamaguchi H, Shinzawa-Itoh K, Nakashima R, Yaono R, Yoshikawa S (1996) Science 272:1136–1144PubMedCrossRefGoogle Scholar
  57. 57.
    Zhou T, Mo Y, Liu A, Zhou Z, Tsai KR (2004) Inorg Chem 43:923–930PubMedCrossRefGoogle Scholar
  58. 58.
    Gray HB, Winkler JR (2003) Q Rev Biophys 36:341–372PubMedCrossRefGoogle Scholar
  59. 59.
    Banci L, Bertini I, Gori Savellini G, Luchinat C (1996) Inorg Chem 35:4248–4253PubMedCrossRefGoogle Scholar
  60. 60.
    Dey A, Jenney FE Jr, Adams MW, Babini E, Takahashi Y, Fukuyama K, Hodgson KO, Hedman B, Solomon EI (2007) Science 318:1464–1468PubMedCrossRefGoogle Scholar
  61. 61.
    Nagashima S, Nakasako M, Dohmae N, Tsujimura M, Takio K, Odaka M, Yohda M, Kamiya N, Endo I (1998) Nat Struct Biol 5:347–351PubMedCrossRefGoogle Scholar
  62. 62.
    Saito MA, Sigman DM, Morel FMM (2003) Inorg Chim Acta 356:308–318CrossRefGoogle Scholar
  63. 63.
    Banerjee R, Ragsdale SW (2003) Annu Rev Biochem 72:209–247PubMedCrossRefGoogle Scholar
  64. 64.
    McCarthy AA, Baker HM, Shewry SC, Patchett ML, Baker EN (2001) Structure 9:637–646PubMedCrossRefGoogle Scholar
  65. 65.
    Mendel RR, Bittner F (2006) Biochim Biophys Acta 1763:621–635PubMedCrossRefGoogle Scholar
  66. 66.
    Hoke KR, Cobb N, Armstrong FA, Hille R (2004) Biochemistry 43:1667–1674PubMedCrossRefGoogle Scholar
  67. 67.
    Ermler U (2005) Dalton Trans 3451–3458Google Scholar
  68. 68.
    Parr RG, Pearson RG (1983) J Am Chem Soc 105:7512–7516CrossRefGoogle Scholar
  69. 69.
    Shannon RD (1976) Acta Crystallogr Sect A 32:751–767CrossRefGoogle Scholar

Copyright information

© SBIC 2008

Authors and Affiliations

  • Claudia Andreini
    • 1
    • 2
  • Ivano Bertini
    • 1
    • 2
  • Gabriele Cavallaro
    • 1
    • 2
  • Gemma L. Holliday
    • 3
  • Janet M. Thornton
    • 3
  1. 1.Magnetic Resonance Center (CERM)University of FlorenceSesto FiorentinoItaly
  2. 2.Department of ChemistryUniversity of FlorenceSesto FiorentinoItaly
  3. 3.EMBL Outstation, Hinxton, European Bioinformatics InstituteCambridgeUK

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