1XC9

Structure of a high-fidelity polymerase bound to a benzo[a]pyrene adduct that blocks replication

1XC9 の概要

• エントリーDOI: 10.2210/pdb1xc9/pdb
• 関連するBIRD辞書のPRD_ID: PRD_900003
• 分子名称: DNA primer strand, DNA template strand with benzo[a]pyrene adduct, DNA polymerase I, ... (8 entities in total)
• 機能のキーワード: dna polymerase i; dna replication; klenow fragment; benzo[a]pyrene; benzopyrene; dna lesion; translation replication, transferase-dna complex, transferase/dna
• 由来する生物種: Geobacillus stearothermophilus
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 74818.99

構造登録者

Hsu, G.W.,Huang, X.,Luneva, N.P.,Geacintov, N.E.,Beese, L.S. (登録日: 2004-09-01, 公開日: 2004-12-14, 最終更新日: 2023-08-23)

主引用文献

Hsu, G.W.,Huang, X.,Luneva, N.P.,Geacintov, N.E.,Beese, L.S.
Structure of a High Fidelity DNA Polymerase Bound to a Benzo[a]pyrene Adduct That Blocks Replication
J.Biol.Chem., 280:3764-3770, 2005

PubMed Abstract: Of the carcinogens to which humans are most frequently exposed, the polycyclic aromatic hydrocarbon benzo[a]pyrene (BP) is one of the most ubiquitous. BP is a byproduct of grilled foods and tobacco and fuel combustion and has long been linked to various human cancers, particularly lung and skin. BP is metabolized to diol epoxides that covalently modify DNA bases to form bulky adducts that block DNA synthesis by replicative or high fidelity DNA polymerases. Here we present the structure of a high fidelity polymerase from a thermostable strain of Bacillus stearothermophilus (Bacillus fragment) bound to the most common BP-derived N2-guanine adduct base-paired with cytosine. The BP adduct adopts a conformation that places the polycyclic BP moiety in the nascent DNA minor groove and is the first structure of a minor groove adduct bound to a polymerase. Orientation of the BP moiety into the nascent DNA minor groove results in extensive disruption to the interactions between the adducted DNA duplex and the polymerase. The disruptions revealed by the structure of Bacillus fragment bound to a BP adduct provide a molecular basis for rationalizing the potent blocking effect on replication exerted by BP adducts.

PubMed: 15548515
DOI: 10.1074/jbc.M411276200

実験手法

X-RAY DIFFRACTION (1.9 Å)