1XC9

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

Summary for 1XC9

• Entry DOI: 10.2210/pdb1xc9/pdb
• Related PRD ID: PRD_900003
• Descriptor: DNA primer strand, DNA template strand with benzo[a]pyrene adduct, DNA polymerase I, ... (8 entities in total)
• Functional Keywords: dna polymerase i; dna replication; klenow fragment; benzo[a]pyrene; benzopyrene; dna lesion; translation replication, transferase-dna complex, transferase/dna
• Biological source: Geobacillus stearothermophilus
• Total number of polymer chains: 3
• Total formula weight: 74818.99

Authors

Hsu, G.W.,Huang, X.,Luneva, N.P.,Geacintov, N.E.,Beese, L.S. (deposition date: 2004-09-01, release date: 2004-12-14, Last modification date: 2023-08-23)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (1.9 Å)