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


We analysed the roles and distribution of metal ions in enzymatic catalysis using available public databases and our new resource Metal-MACiE ( 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.


Metal Enzyme Metalloenzyme Database Catalysis 



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).


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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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