4KLM

DNA polymerase beta matched product complex with Mg2+, 11 h

4KLM の概要

• エントリーDOI: 10.2210/pdb4klm/pdb
• 関連するPDBエントリー: 4KLD 4KLE 4KLF 4KLG 4KLH 4KLI 4KLJ 4KLL 4KLO 4KLP 4KLQ 4KLS 4KLT 4KLU
• 分子名称: 5'-D(*CP*CP*GP*AP*CP*GP*GP*CP*GP*CP*AP*TP*CP*AP*GP*C)-3', 5'-D(*GP*CP*TP*GP*AP*TP*GP*CP*GP*CP*C)-3', 5'-D(P*GP*TP*CP*GP*G)-3', ... (9 entities in total)
• 機能のキーワード: dna polymerase, transferase, lyase-dna complex, lyase/dna
• 由来する生物種: Homo sapiens (human)
• 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: 48339.21

構造登録者

Freudenthal, B.D.,Beard, W.A.,Shock, D.D.,Wilson, S.H. (登録日: 2013-05-07, 公開日: 2013-07-17, 最終更新日: 2023-09-20)

主引用文献

Freudenthal, B.D.,Beard, W.A.,Shock, D.D.,Wilson, S.H.
Observing a DNA polymerase choose right from wrong.
Cell(Cambridge,Mass.), 154:157-168, 2013

PubMed Abstract: DNA polymerase (pol) β is a model polymerase involved in gap-filling DNA synthesis utilizing two metals to facilitate nucleotidyl transfer. Previous structural studies have trapped catalytic intermediates by utilizing substrate analogs (dideoxy-terminated primer or nonhydrolysable incoming nucleotide). To identify additional intermediates during catalysis, we now employ natural substrates (correct and incorrect nucleotides) and follow product formation in real time with 15 different crystal structures. We are able to observe molecular adjustments at the active site that hasten correct nucleotide insertion and deter incorrect insertion not appreciated previously. A third metal binding site is transiently formed during correct, but not incorrect, nucleotide insertion. Additionally, long incubations indicate that pyrophosphate more easily dissociates after incorrect, compared to correct, nucleotide insertion. This appears to be coupled to subdomain repositioning that is required for catalytic activation/deactivation. The structures provide insights into a fundamental chemical reaction that impacts polymerase fidelity and genome stability.

PubMed: 23827680
DOI: 10.1016/j.cell.2013.05.048

実験手法

X-RAY DIFFRACTION (1.747 Å)