An incoming nucleotide imposes an anti to syn conformational change on the templating purine in the human DNA polymerase-iota active site

Structure. 2006 Apr;14(4):749-55. doi: 10.1016/j.str.2006.01.010.


Substrate-induced conformational change of the protein is the linchpin of enzymatic reactions. Replicative DNA polymerases, for example, convert from an open to a closed conformation in response to dNTP binding. Human DNA polymerase-iota (hPoliota), a member of the Y family of DNA polymerases, differs strikingly from other polymerases in its much higher proficiency and fidelity for nucleotide incorporation opposite template purines than opposite template pyrimidines. We present here a crystallographic analysis of hPoliota binary complexes, which together with the ternary complexes show that, contrary to replicative DNA polymerases, the DNA, and not the polymerase, undergoes the primary substrate-induced conformational change. The incoming dNTP "pushes" templates A and G from the anti to the syn conformation dictated by a rigid hPoliota active site. Together, the structures posit a mechanism for template selection wherein dNTP binding induces a conformational switch in template purines for productive Hoogsteen base pairing.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Base Pairing
  • Binding Sites
  • Crystallography, X-Ray
  • DNA / chemistry
  • DNA Polymerase iota
  • DNA Replication
  • DNA-Directed DNA Polymerase / chemistry*
  • Glutathione Transferase / metabolism
  • Models, Chemical
  • Models, Molecular
  • Molecular Conformation
  • Nucleotides / chemistry*
  • Protein Binding
  • Protein Conformation
  • Protein Structure, Tertiary
  • Purines / chemistry
  • Recombinant Fusion Proteins / chemistry


  • Nucleotides
  • Purines
  • Recombinant Fusion Proteins
  • DNA
  • Glutathione Transferase
  • DNA-Directed DNA Polymerase
  • DNA Polymerase iota

Associated data

  • PDB/2FLL
  • PDB/2FLN
  • PDB/2FLP