5DB8

Structure of human DNA polymerase beta Host-Guest complex with the N7MG base paired with a dA

Summary for 5DB8

• Entry DOI: 10.2210/pdb5db8/pdb
• Related: 5DB6 5DB7 5DB9 5DBA 5DBB 5DBC
• Descriptor: DNA polymerase beta, DNA (5'-D(*CP*CP*GP*AP*CP*GP*TP*CP*GP*CP*AP*TP*AP*AP*GP*C)-3'), DNA (5'-D(*GP*CP*TP*(FMG)P*AP*TP*GP*CP*GP*A)-3'), ... (6 entities in total)
• Functional Keywords: human dna polymerase, transferase-dna complex, transferase/dna
• Biological source: Homo sapiens (Human); More
• Cellular location: Nucleus: P06746
• Total number of polymer chains: 4
• Total formula weight: 47809.91

Authors

Koag, M.C.,Lee, S. (deposition date: 2015-08-21, release date: 2015-11-11, Last modification date: 2024-03-13)

Primary citation

Kou, Y.,Koag, M.C.,Lee, S.
N7 Methylation Alters Hydrogen-Bonding Patterns of Guanine in Duplex DNA.
J.Am.Chem.Soc., 137:14067-14070, 2015

PubMed Abstract: 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 polβ-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 polβ-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.

PubMed: 26517568
DOI: 10.1021/jacs.5b10172

Experimental method

X-RAY DIFFRACTION (2.547 Å)