DNA polymerase beta catalytic efficiency mirrors the Asn279-dCTP H-bonding strength

FEBS Lett. 2007 Feb 20;581(4):775-80. doi: 10.1016/j.febslet.2007.01.042. Epub 2007 Jan 25.


Ternary complexes of wild type or mutant form of human DNA polymerase beta (pol beta) bound to DNA and dCTP substrates were studied by molecular dynamics (MD) simulations. The occurrences of contact configurations (CC) of structurally important atom pairs were sampled along the MD trajectories, and converted into free-energy differences, DeltaG(CC). DeltaG(CC) values were correlated with the experimental binding and catalytic free energies for the wild type pol beta and its Arg183Ala, Tyr271Ala, Asp276Val, Lys280Gly, Arg283Ala, and Glu295Ala mutants. The correlation coefficients show that the strength of the H-bond between dCTP and Asn279 is a strong predictor of the mutation-induced changes in the catalytic efficiency of pol beta. This finding is consistent with the view that enzyme preorganization plays a major role in controlling DNA polymerase specific activity.

Publication types

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

MeSH terms

  • Asparagine / metabolism*
  • Binding Sites
  • Catalysis
  • DNA Polymerase beta / chemistry*
  • DNA Polymerase beta / metabolism*
  • DNA Primers / metabolism
  • Deoxycytosine Nucleotides / metabolism*
  • Humans
  • Hydrogen Bonding
  • Static Electricity
  • Structure-Activity Relationship
  • Thermodynamics


  • DNA Primers
  • Deoxycytosine Nucleotides
  • 2'-deoxycytidine 5'-triphosphate
  • Asparagine
  • DNA Polymerase beta