Solution structure of a viral DNA repair polymerase.
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.
Maciejewski
M W
MW
Department of Biochemistry, University of Connecticut Health Center, 263 Farmington Avenue, Farmington, Connecticut 06032, USA.
Shin
R
R
Pan
B
B
Marintchev
A
A
Denninger
A
A
Mullen
M A
MA
Chen
K
K
Gryk
M R
MR
Mullen
G P
GP
D000358:African Swine Fever Virus / Q000201:enzymology*; D000595:Amino Acid Sequence; D001483:Base Sequence; D001665:Binding Sites; D004247:DNA / Q000235:genetics / Q000378:metabolism; D019951:DNA Polymerase beta / Q000737:chemistry; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism; D004259:DNA-Directed DNA Polymerase / Q000737:chemistry* / Q000378:metabolism; D008274:Magnesium / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D019906:Nuclear Magnetic Resonance, Biomolecular; D009711:Nucleotides / Q000378:metabolism; D017433:Protein Structure, Secondary; D016415:Sequence Alignment; D012996:Solutions; D013050:Spectrometry, Fluorescence; D013329:Structure-Activity Relationship; D013379:Substrate Specificity
D004268:DNA-Binding Proteins; D009711:Nucleotides; D012996:Solutions; D004247:DNA; C109534:DNA polymerase X; D019951:DNA Polymerase beta; D004259:DNA-Directed DNA Polymerase; D008274:Magnesium