Making and breaking nucleic acids: two-Mg2+-ion catalysis and substrate specificity

Mol Cell. 2006 Apr 7;22(1):5-13. doi: 10.1016/j.molcel.2006.03.013.


DNA and a large proportion of RNA are antiparallel duplexes composed of an unvarying phosphosugar backbone surrounding uniformly stacked and highly similar base pairs. How do the myriad of enzymes (including ribozymes) that perform catalysis on nucleic acids achieve exquisite structure or sequence specificity? In all DNA and RNA polymerases and many nucleases and transposases, two Mg2+ ions are jointly coordinated by the nucleic acid substrate and catalytic residues of the enzyme. Based on the exquisite sensitivity of Mg2+ ions to the ligand geometry and electrostatic environment, we propose that two-metal-ion catalysis greatly enhances substrate recognition and catalytic specificity.

Publication types

  • Research Support, N.I.H., Intramural
  • Review

MeSH terms

  • Catalysis
  • DNA-Directed DNA Polymerase / metabolism
  • DNA-Directed RNA Polymerases / metabolism
  • Deoxyribonucleases / metabolism
  • Magnesium / chemistry*
  • Magnesium / metabolism
  • Models, Molecular
  • Nucleic Acid Conformation
  • Nucleic Acids / chemistry*
  • Nucleic Acids / metabolism
  • RNA, Catalytic / metabolism
  • Ribonucleases / metabolism
  • Substrate Specificity
  • Transposases / metabolism


  • Nucleic Acids
  • RNA, Catalytic
  • Transposases
  • DNA-Directed RNA Polymerases
  • DNA-Directed DNA Polymerase
  • Deoxyribonucleases
  • Ribonucleases
  • Magnesium