1xc9
From Proteopedia
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Structure of a high-fidelity polymerase bound to a benzo[a]pyrene adduct that blocks replication
Overview
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.
About this Structure
1XC9 is a Protein complex structure of sequences from Geobacillus stearothermophilus with SUC, SO4, MG and BAP as ligands. Active as DNA-directed DNA polymerase, with EC number 2.7.7.7 Full crystallographic information is available from OCA.
Reference
Structure of a high fidelity DNA polymerase bound to a benzo[a]pyrene adduct that blocks replication., Hsu GW, Huang X, Luneva NP, Geacintov NE, Beese LS, J Biol Chem. 2005 Feb 4;280(5):3764-70. Epub 2004 Nov 16. PMID:15548515[[Category: dna polymerase i; dna replication; klenow fragment; benzo[a]pyrene; benzopyrene; dna lesion; translation replication]]
Page seeded by OCA on Sun Nov 25 01:50:24 2007
