Interaction of dNTP, pyrophosphate and their analogs with the dNTP-binding sites of E. coli DNA polymerase I Klenow fragment and human DNA polymerase alpha

FEBS Lett. 1990 Dec 17;277(1-2):194-6. doi: 10.1016/0014-5793(90)80842-7.

Abstract

The 3',5'-exonuclease center of the Klenow fragment of E. coli DNA polymerase I (FK) was selectively blocked by NaF. The latter was shown to forbid the binding of nucleotides and their analogs to the enzyme exonuclease center. In the presence of poly(dT).r(pA)10 template.primer complex and NaF, we observed AMP, ADP, ATP, PPi and dATP to be competitive inhibitors of the FK-catalyzed DNA polymerization. The interactions of the nucleotides with FK and human DNA polymerase alpha were compared to reveal similarity of binding to the DNA polymerizing centers. Structural components of dNTP and PPi playing key roles in forming complexes with pro- and eukaryotic DNA polymerases were identified.

MeSH terms

  • Adenosine Monophosphate / metabolism
  • Binding Sites
  • DNA / biosynthesis
  • DNA Polymerase I / metabolism*
  • DNA Polymerase II / metabolism*
  • Deoxyribonucleotides / metabolism*
  • Diphosphates / metabolism*
  • Escherichia coli / enzymology
  • Humans
  • In Vitro Techniques
  • Kinetics
  • Ligands
  • Protein Binding
  • Sodium Fluoride / pharmacology
  • Substrate Specificity

Substances

  • Deoxyribonucleotides
  • Diphosphates
  • Ligands
  • Adenosine Monophosphate
  • Sodium Fluoride
  • DNA
  • DNA Polymerase I
  • DNA Polymerase II