9DDR

Ternary substrate complex of DNA polymerase iota with DNA (template A), Ca2+, and dTTP

9DDR の概要

• エントリーDOI: 10.2210/pdb9ddr/pdb
• 分子名称: DNA polymerase iota, DNA (5'-D(P*AP*AP*GP*GP*GP*TP*CP*CP*TP*AP*GP*GP*AP*CP*CP*C)-3'), THYMIDINE-5'-TRIPHOSPHATE, ... (5 entities in total)
• 機能のキーワード: dna, polymerase, lesion, replication
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 53091.24

構造登録者

Frevert, Z.,Reusch, D.,Freudenthal, B.,Washington, M.T. (登録日: 2024-08-28, 公開日: 2025-07-09, 最終更新日: 2025-07-16)

主引用文献

Frevert, Z.,Reusch, D.T.,Gildenberg, M.S.,Jordan, S.M.,Ryan, B.J.,Freudenthal, B.D.,Washington, M.T.
Visualizing DNA polymerase iota catalyze Hoogsteen-directed DNA synthesis.
Nat Commun, 16:5979-5979, 2025

PubMed Abstract: Translesion synthesis polymerases efficiently incorporate nucleotides opposite DNA lesions. Pol ι, for example, bypasses minor-groove and exocyclic purine adducts. Conventional X-ray crystallography showed that this enzyme incorporates nucleotides by forming Hoogsteen base pairs with the incoming nucleotide rather than Watson-Crick base pairs. While this revealed the structural basis of nucleotide selection during nucleotide binding, it did not allow the visualization of the process of phosphodiester bond formation or the detection of reaction intermediates that form during nucleotide incorporation. Here, we use a combination of time-lapse crystallography and molecular dynamics simulations to examine the mechanism of pol ι-catalyzed nucleotide incorporation. We show that this enzyme maintains Hoogsteen base pairing with the incoming dNTP during the entire reaction. We also show that pol ι possesses a pyrophosphatase activity that generates two monophosphates within its active site. Our findings provide insights into the features of pol ι's active site that allow it to translocate along DNA and catalyze processive DNA synthesis.

PubMed: 40593703
DOI: 10.1038/s41467-025-61245-8

実験手法

X-RAY DIFFRACTION (2.15 Å)