4PHD

Structure of human DNA polymerase beta complexed with A in the template base paired with incoming non-hydrolyzable CTP and MANGANESE

4PHD の概要

• エントリーDOI: 10.2210/pdb4phd/pdb
• 分子名称: DNA polymerase beta, DNA (5'-D(*CP*CP*GP*AP*CP*AP*TP*CP*GP*CP*AP*TP*CP*AP*GP*C)-3'), DNA (5'-D(*GP*CP*TP*GP*AP*TP*GP*CP*GP*A)-3'), ... (8 entities in total)
• 機能のキーワード: human dna polymerase beta, transferase, lyase-dna complex, lyase/dna
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 47608.01

構造登録者

Koag, M.C.,Lee, S. (登録日: 2014-05-06, 公開日: 2014-09-24, 最終更新日: 2023-12-27)

主引用文献

Koag, M.C.,Nam, K.,Lee, S.
The spontaneous replication error and the mismatch discrimination mechanisms of human DNA polymerase beta.
Nucleic Acids Res., 42:11233-11245, 2015

PubMed Abstract: To provide molecular-level insights into the spontaneous replication error and the mismatch discrimination mechanisms of human DNA polymerase β (polβ), we report four crystal structures of polβ complexed with dG•dTTP and dA•dCTP mismatches in the presence of Mg2+ or Mn2+. The Mg(2+)-bound ground-state structures show that the dA•dCTP-Mg2+ complex adopts an 'intermediate' protein conformation while the dG•dTTP-Mg2+ complex adopts an open protein conformation. The Mn(2+)-bound 'pre-chemistry-state' structures show that the dA•dCTP-Mn2+ complex is structurally very similar to the dA•dCTP-Mg2+ complex, whereas the dG•dTTP-Mn2+ complex undergoes a large-scale conformational change to adopt a Watson-Crick-like dG•dTTP base pair and a closed protein conformation. These structural differences, together with our molecular dynamics simulation studies, suggest that polβ increases replication fidelity via a two-stage mismatch discrimination mechanism, where one is in the ground state and the other in the closed conformation state. In the closed conformation state, polβ appears to allow only a Watson-Crick-like conformation for purine•pyrimidine base pairs, thereby discriminating the mismatched base pairs based on their ability to form the Watson-Crick-like conformation. Overall, the present studies provide new insights into the spontaneous replication error and the replication fidelity mechanisms of polβ.

PubMed: 25200079
DOI: 10.1093/nar/gku789

実験手法

X-RAY DIFFRACTION (2.21 Å)