4U7C

Structure of DNA polymerase kappa in complex with benzopyrene adducted DNA

4U7C の概要

• エントリーDOI: 10.2210/pdb4u7c/pdb
• 関連するPDBエントリー: 4U6P
• 分子名称: DNA polymerase kappa, DNA (5'-D(P*GP*CP*GP*GP*AP*TP*CP*AP*G)-3'), DNA (5'-D(*P*AP*TP*GP*(VKJ)P*CP*TP*GP*AP*TP*CP*CP*GP*C)-3'), ... (8 entities in total)
• 機能のキーワード: benzo[a]pyrene-n2-guanine, dna replication, dna damage tolerance, polymerase kappa, environment pollution, transferase-dna complex, transferase/dna
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 127741.36

構造登録者

Jha, V.K.,Ling, H. (登録日: 2014-07-30, 公開日: 2016-01-27, 最終更新日: 2023-09-27)

主引用文献

Jha, V.,Bian, C.,Xing, G.,Ling, H.
Structure and mechanism of error-free replication past the major benzo[a]pyrene adduct by human DNA polymerase kappa.
Nucleic Acids Res., 44:4957-4967, 2016

PubMed Abstract: Benzo[a]pyrene (BP) is a well-known and frequently encountered carcinogen which generates a bulky DNA adduct (+)-trans-10S-BP-N(2)-dG (BP-dG) in cells. DNA polymerase kappa (polκ) is the only known Y-family polymerase that bypasses BP-dG accurately and thus protects cells from genotoxic BP. Here, we report the structures of human polκ in complex with DNA containing either a normal guanine (G) base or a BP-dG adduct at the active site and a correct deoxycytidine. The structures and supporting biochemical data reveal a unique mechanism for accurate replication by translesion synthesis past the major bulky adduct. The active site of polκ opens at the minor groove side of the DNA substrate to accommodate the bulky BP-dG that is attached there. More importantly, polκ stabilizes the lesion DNA substrate in the same active conformation as for regular B-form DNA substrates and the bulky BPDE ring in a 5' end pointing conformation. The BP-dG adducted DNA substrate maintains a Watson-Crick (BP-dG:dC) base pair within the active site, governing correct nucleotide insertion opposite the bulky adduct. In addition, polκ's unique N-clasp domain supports the open conformation of the enzyme and the extended conformation of the single-stranded template to allow bypass of the bulky lesion. This work illustrates the first molecular mechanism for how a bulky major adduct is replicated accurately without strand misalignment and mis-insertion.

PubMed: 27034468
DOI: 10.1093/nar/gkw204

実験手法

X-RAY DIFFRACTION (2.8 Å)