5TWS

Post-catalytic complex of human Polymerase Mu (H329A) with newly incorporated UTP

5TWS の概要

• エントリーDOI: 10.2210/pdb5tws/pdb
• 関連するPDBエントリー: 5TWP 5TWQ 5TWR
• 分子名称: human DNA Polymerase Mu, 4-(2-HYDROXYETHYL)-1-PIPERAZINE ETHANESULFONIC ACID, DNA (5'-D(*CP*GP*GP*CP*AP*TP*AP*CP*G)-3'), ... (11 entities in total)
• 機能のキーワード: family x dna polymerase, nonhomologous end-joining, dna double strand break repair, ribonucleotide incorporation, transferase-dna complex, transferase/dna
• 由来する生物種: Homo sapiens; 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 45795.24

構造登録者

Moon, A.F.,Pryor, J.M.,Ramsden, D.A.,Kunkel, T.A.,Bebenek, K.,Pedersen, L.C. (登録日: 2016-11-14, 公開日: 2017-07-05, 最終更新日: 2023-11-15)

主引用文献

Moon, A.F.,Pryor, J.M.,Ramsden, D.A.,Kunkel, T.A.,Bebenek, K.,Pedersen, L.C.
Structural accommodation of ribonucleotide incorporation by the DNA repair enzyme polymerase Mu.
Nucleic Acids Res., 45:9138-9148, 2017

PubMed Abstract: While most DNA polymerases discriminate against ribonucleotide triphosphate (rNTP) incorporation very effectively, the Family X member DNA polymerase μ (Pol μ) incorporates rNTPs almost as efficiently as deoxyribonucleotides. To gain insight into how this occurs, here we have used X-ray crystallography to describe the structures of pre- and post-catalytic complexes of Pol μ with a ribonucleotide bound at the active site. These structures reveal that Pol μ binds and incorporates a rNTP with normal active site geometry and no distortion of the DNA substrate or nucleotide. Moreover, a comparison of rNTP incorporation kinetics by wildtype and mutant Pol μ indicates that rNTP accommodation involves synergistic interactions with multiple active site residues not found in polymerases with greater discrimination. Together, the results are consistent with the hypothesis that rNTP incorporation by Pol μ is advantageous in gap-filling synthesis during DNA double strand break repair by nonhomologous end joining, particularly in nonreplicating cells containing very low deoxyribonucleotide concentrations.

PubMed: 28911097
DOI: 10.1093/nar/gkx527

実験手法

X-RAY DIFFRACTION (1.85 Å)