1xc9

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{{STRUCTURE_1xc9| PDB=1xc9 | SCENE= }}
{{STRUCTURE_1xc9| PDB=1xc9 | SCENE= }}
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'''Structure of a high-fidelity polymerase bound to a benzo[a]pyrene adduct that blocks replication'''
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===Structure of a high-fidelity polymerase bound to a benzo[a]pyrene adduct that blocks replication===
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==Overview==
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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.
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(as it appears on PubMed at http://www.pubmed.gov), where 15548515 is the PubMed ID number.
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{{ABSTRACT_PUBMED_15548515}}
==About this Structure==
==About this Structure==
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[[Category: Klenow fragment]]
[[Category: Klenow fragment]]
[[Category: Translation replication]]
[[Category: Translation replication]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 14:50:39 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Jul 27 18:47:02 2008''

Revision as of 15:47, 27 July 2008

Image:1xc9.png

Template:STRUCTURE 1xc9

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

Template:ABSTRACT PUBMED 15548515

About this Structure

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

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