3C2L

Ternary complex of DNA POLYMERASE BETA with a C:DAPCPP mismatch in the active site

3C2L の概要

• エントリーDOI: 10.2210/pdb3c2l/pdb
• 関連するPDBエントリー: 2FMP 3C2K 3C2M
• 分子名称: DNA (5'-D(*DCP*DCP*DGP*DAP*DCP*DCP*DGP*DCP*DGP*DCP*DAP*DTP*DCP*DAP*DGP*DC)-3'), DNA (5'-D(*DGP*DCP*DTP*DGP*DAP*DTP*DGP*DCP*DGP*DC)-3'), DNA (5'-D(P*DGP*DTP*DCP*DGP*DG)-3'), ... (8 entities in total)
• 機能のキーワード: nucleotidyl transferase, dna polymerase, misincorporation, dna damage, dna repair, dna replication, dna synthesis, dna-binding, dna-directed dna polymerase, lyase, magnesium, metal-binding, nucleotidyltransferase, nucleus, polymorphism, sodium, transferase-dna complex, transferase/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: 48532.66

構造登録者

Batra, V.K.,Beard, W.A.,Shock, D.D.,Pedersen, L.C.,Wilson, S.H. (登録日: 2008-01-25, 公開日: 2008-05-20, 最終更新日: 2023-08-30)

主引用文献

Batra, V.K.,Beard, W.A.,Shock, D.D.,Pedersen, L.C.,Wilson, S.H.
Structures of DNA polymerase beta with active-site mismatches suggest a transient abasic site intermediate during misincorporation.
Mol.Cell, 30:315-324, 2008

PubMed Abstract: We report the crystallographic structures of DNA polymerase beta with dG-dAMPCPP and dC-dAMPCPP mismatches in the active site. These premutagenic structures were obtained with a nonhydrolyzable incoming nucleotide analog, dAMPCPP, and Mn(2+). Substituting Mn(2+) for Mg(2+) significantly decreases the fidelity of DNA synthesis. The structures reveal that the enzyme is in a closed conformation like that observed with a matched Watson-Crick base pair. The incorrect dAMPCPP binds in a conformation identical to that observed with the correct nucleotide. To accommodate the incorrect nucleotide and closed protein conformation, the template strand in the vicinity of the active site has shifted upstream over 3 A, removing the coding base from the active site and generating an abasic templating pocket. The primer terminus rotates as its complementary template base is repositioned. This rotation moves O3' of the primer terminus away from the alpha-phosphate of the incoming nucleotide, thereby deterring misincorporation.

PubMed: 18471977
DOI: 10.1016/j.molcel.2008.02.025

実験手法

X-RAY DIFFRACTION (2.6 Å)