5DB8: Structure Of Human Dna Polymerase Beta Host-guest Complex With The N7mg Base Paired With A Da

N7-Alkyl-2'-deoxyguanosines are major adducts in DNA that are generated by various alkylating mutagens and drugs. However, the effect of the N7 alkylation on the hydrogen-bonding patterns of the guanine remains poorly understood. We prepared N7-methyl-2'-deoxyguanosine (N7mdG)-containing DNA using a transition-state destabilization strategy, developed a novel polbeta-host-guest complex system, and determined eight crystal structures of N7mdG or dG paired with dC, dT, dG, and dA. The structures of N7mdG:dC and N7mdG:dG are very similar to those of dG:dC and dG:dG, respectively, indicating the involvement of the keto tautomeric form of N7mdG in the base pairings with dC and dG. On the other hand, the structure of N7mdG:dT shows that the mispair forms three hydrogen bonds and adopts a Watson-Crick-like geometry rather than a wobble geometry, suggesting that the enol tautomeric form of N7mdG involves in its base pairing with dT. In addition, N7mdG:dA adopts a novel shifted anti:syn base pair presumably via the enol tautomeric form of N7mdG. The polbeta-host-guest complex structures reveal that guanine-N7 methylation changes the hydrogen-bonding patterns of the guanine when paired with dT or dA and suggest that N7 alkylation may alter the base pairing patterns of guanine by promoting the formation of the rare enol tautomeric form of guanine.
PDB ID: 5DB8Download
MMDB ID: 134128
PDB Deposition Date: 2015/8/21
Updated in MMDB: 2015/11
Experimental Method:
x-ray diffraction
Resolution: 2.55  Å
Similar Structures:
Biological Unit for 5DB8: tetrameric; determined by author and by software (PISA)
Molecular Components in 5DB8
Label Count Molecule
Protein (1 molecule)
DNA Polymerase Beta(Gene symbol: POLB)
Molecule annotation
Nucleotides(3 molecules)
DNA (5'-d(*cp*cp*gp*ap*cp*gp*tp*cp*gp*cp*ap*tp*ap*ap*gp*c)- 3')
Molecule annotation
DNA (5'-d(*gp*cp*tp*(fmg)p*ap*tp*gp*cp*gp*a)-3')
Molecule annotation
DNA (5'-d(p*gp*tp*cp*gp*g)-3')
Molecule annotation
Chemicals (2 molecules)
* Click molecule labels to explore molecular sequence information.

Citing MMDB