4M47

structure of human DNA polymerase complexed with 8-BrG in the template base paired with incoming non-hydrolyzable GTP

4M47 の概要

• エントリーDOI: 10.2210/pdb4m47/pdb
• 関連するPDBエントリー: 1BPX 3ISB 4M2Y
• 分子名称: DNA polymerase beta, a synthetic template, a synthetic upstream primer, ... (8 entities in total)
• 機能のキーワード: dna synthesis, base excision repair, transferase-dna complex, transferase/dna
• 由来する生物種: Homo sapiens (human); 詳細
• 細胞内の位置: Nucleus: P06746
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 47111.73

構造登録者

Koag, M.C.,Min, K.,Monzingo, A.F.,Lee, S. (登録日: 2013-08-06, 公開日: 2014-01-22, 最終更新日: 2024-02-28)

主引用文献

Koag, M.C.,Min, K.,Lee, S.
Structural basis for promutagenicity of 8-halogenated Guanine.
J.Biol.Chem., 289:6289-6298, 2014

PubMed Abstract: 8-Halogenated guanine (haloG), a major DNA adduct formed by reactive halogen species during inflammation, is a promutagenic lesion that promotes misincorporation of G opposite the lesion by various DNA polymerases. Currently, the structural basis for such misincorporation is unknown. To gain insights into the mechanism of misincorporation across haloG by polymerase, we determined seven x-ray structures of human DNA polymerase β (polβ) bound to DNA bearing 8-bromoguanine (BrG). We determined two pre-catalytic ternary complex structures of polβ with an incoming nonhydrolyzable dGTP or dCTP analog paired with templating BrG. We also determined five binary complex structures of polβ in complex with DNA containing BrG·C/T at post-insertion and post-extension sites. In the BrG·dGTP ternary structure, BrG adopts syn conformation and forms Hoogsteen base pairing with the incoming dGTP analog. In the BrG·dCTP ternary structure, BrG adopts anti conformation and forms Watson-Crick base pairing with the incoming dCTP analog. In addition, our polβ binary post-extension structures show Hoogsteen BrG·G base pair and Watson-Crick BrG·C base pair. Taken together, the first structures of haloG-containing DNA bound to a protein indicate that both BrG·G and BrG·C base pairs are accommodated in the active site of polβ. Our structures suggest that Hoogsteen-type base pairing between G and C8-modified G could be accommodated in the active site of a DNA polymerase, promoting G to C mutation.

PubMed: 24425881
DOI: 10.1074/jbc.M113.537803

実験手法

X-RAY DIFFRACTION (2.37 Å)