7M4C

DNA Polymerase Lambda, TTP:At Mn2+ Product State Ternary Complex, 960 min

7M4C の概要

• エントリーDOI: 10.2210/pdb7m4c/pdb
• 分子名称: DNA polymerase lambda, DNA (5'-D(*CP*GP*GP*CP*AP*GP*TP*AP*CP*TP*G)-3'), DNA (5'-D(*CP*AP*GP*TP*AP*CP*T)-3'), ... (9 entities in total)
• 機能のキーワード: time-lapse crystallography, double strand break repair, dna synthesis fidelity, replication
• 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: 44089.51

構造登録者

Jamsen, J.A.,Wilson, S.H. (登録日: 2021-03-21, 公開日: 2022-07-06, 最終更新日: 2023-10-18)

主引用文献

Jamsen, J.A.,Shock, D.D.,Wilson, S.H.
Watching right and wrong nucleotide insertion captures hidden polymerase fidelity checkpoints.
Nat Commun, 13:3193-3193, 2022

PubMed Abstract: Efficient and accurate DNA synthesis is enabled by DNA polymerase fidelity checkpoints that promote insertion of the right instead of wrong nucleotide. Erroneous X-family polymerase (pol) λ nucleotide insertion leads to genomic instability in double strand break and base-excision repair. Here, time-lapse crystallography captures intermediate catalytic states of pol λ undergoing right and wrong natural nucleotide insertion. The revealed nucleotide sensing mechanism responds to base pair geometry through active site deformation to regulate global polymerase-substrate complex alignment in support of distinct optimal (right) or suboptimal (wrong) reaction pathways. An induced fit during wrong but not right insertion, and associated metal, substrate, side chain and pyrophosphate reaction dynamics modulated nucleotide insertion. A third active site metal hastened right but not wrong insertion and was not essential for DNA synthesis. The previously hidden fidelity checkpoints uncovered reveal fundamental strategies of polymerase DNA repair synthesis in genomic instability.

PubMed: 35680862
DOI: 10.1038/s41467-022-30141-w

実験手法

X-RAY DIFFRACTION (1.95 Å)