Solution structure of a viral DNA repair polymerase

Nat Struct Biol. 2001 Nov;8(11):936-41. doi: 10.1038/nsb1101-936.

Abstract

DNA polymerase X (Pol X) from the African swine fever virus (ASFV) specifically binds intermediates in the single-nucleotide base-excision repair process, an activity indicative of repair function. In addition, Pol X catalyzes DNA polymerization with low nucleotide-insertion fidelity. The structural mechanisms by which DNA polymerases confer high or low fidelity in DNA polymerization remain to be elucidated. The three-dimensional structure of Pol X has been determined. Unlike other DNA polymerases, Pol X is formed from only a palm and a C-terminal subdomain. Pol X has a novel palm subdomain fold, containing a positively charged helix at the DNA binding surface. Purine deoxynucleoside triphosphate (dNTP) substrates bind between the palm and C-terminal subdomain, at a dNTP-binding helix, and induce a unique conformation in Pol X. The purine dNTP-bound conformation and high binding affinity for dGTP-Mg(2+) of Pol X may contribute to its low fidelity.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • African Swine Fever Virus / enzymology*
  • Amino Acid Sequence
  • Base Sequence
  • Binding Sites
  • DNA / genetics
  • DNA / metabolism
  • DNA Polymerase beta / chemistry
  • DNA-Binding Proteins / chemistry
  • DNA-Binding Proteins / metabolism
  • DNA-Directed DNA Polymerase / chemistry*
  • DNA-Directed DNA Polymerase / metabolism
  • Magnesium / metabolism
  • Models, Molecular
  • Molecular Sequence Data
  • Nuclear Magnetic Resonance, Biomolecular
  • Nucleotides / metabolism
  • Protein Structure, Secondary
  • Sequence Alignment
  • Solutions
  • Spectrometry, Fluorescence
  • Structure-Activity Relationship
  • Substrate Specificity

Substances

  • DNA-Binding Proteins
  • Nucleotides
  • Solutions
  • DNA
  • DNA polymerase X
  • DNA Polymerase beta
  • DNA-Directed DNA Polymerase
  • Magnesium

Associated data

  • PDB/1JAJ