Mutagenic conformation of 8-oxo-7,8-dihydro-2'-dGTP in the confines of a DNA polymerase active site.
The major product of oxidative base damage is 8-oxo-7,8-dihydro-2'-deoxyguanine (8odG). The coding potential of this lesion is modulated by its glycosidic torsion angle that controls whether its Watson-Crick or Hoogsteen edge is used for base pairing. The 2.0-A structure of DNA polymerase (pol) beta bound with 8odGTP opposite template adenine indicates that the modified nucleotide assumes the mutagenic syn conformation and that the nonmutagenic anti conformation would be incompatible with efficient DNA synthesis.
Laboratory of Structural Biology, National Institute of Environmental Health Sciences, US National Institutes of Health, Research Triangle Park, North Carolina, USA.
Vinod K
VK
Batra
William A
WA
Beard
Esther W
EW
Hou
Lars C
LC
Pedersen
Rajendra
R
Prasad
Samuel H
SH
Wilson
D000080242:8-Hydroxy-2'-Deoxyguanosine / Q000031:analogs & derivatives; D020134:Catalytic Domain; D018360:Crystallography, X-Ray; D019951:DNA Polymerase beta / Q000737:chemistry* / Q000378:metabolism; D006147:Guanine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D008958:Models, Molecular; D008968:Molecular Conformation; D011487:Protein Conformation
D006147:Guanine; C078307:8-oxo-7,8-dihydrodeoxyguanine; D000080242:8-Hydroxy-2'-Deoxyguanosine; D019951:DNA Polymerase beta