Mode of inhibition of the DNA polymerase of Methanococcus vannielii by aphidicolin

Eur J Biochem. 1987 May 15;165(1):171-5. doi: 10.1111/j.1432-1033.1987.tb11208.x.

Abstract

The mode of action of aphidicolin on DNA synthesis catalysed by the DNA polymerase of Methanococcus vannielii is competitive for dCTP, noncompetitive for dATP, dGTP and dTTP and uncompetitive for activated DNA. The kinetic data are accounted for by a mechanism in which dCTP and aphidicolin compete for the dCTP-specific binding site on the DNA polymerase. The dissociation constant for the aphidicolin--DNA-polymerase complex is 0.04-0.07 microM. Similar modes of inhibition of DNA synthesis exist for DNA polymerase alpha of higher eucaryotes but not for eubacteria or viruses and suggests a close functional relationship between the DNA polymerase of eucaryotes and of the archaebacterium M. vannielii.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aphidicolin
  • Binding Sites
  • DNA Replication / drug effects
  • Diterpenes / pharmacology*
  • Euryarchaeota / enzymology*
  • Kinetics
  • Nucleic Acid Synthesis Inhibitors*
  • Protein Binding
  • Substrate Specificity

Substances

  • Diterpenes
  • Nucleic Acid Synthesis Inhibitors
  • Aphidicolin