1xc9
From Proteopedia
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[[Image:1xc9.gif|left|200px]] | [[Image:1xc9.gif|left|200px]] | ||
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'''Structure of a high-fidelity polymerase bound to a benzo[a]pyrene adduct that blocks replication''' | '''Structure of a high-fidelity polymerase bound to a benzo[a]pyrene adduct that blocks replication''' | ||
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==About this Structure== | ==About this Structure== | ||
- | + | Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1XC9 OCA]. | |
==Reference== | ==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:[http://www.ncbi.nlm.nih.gov/pubmed/15548515 15548515] | 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:[http://www.ncbi.nlm.nih.gov/pubmed/15548515 15548515] | ||
[[Category: DNA-directed DNA polymerase]] | [[Category: DNA-directed DNA polymerase]] | ||
- | [[Category: Geobacillus stearothermophilus]] | ||
- | [[Category: Protein complex]] | ||
[[Category: Beese, L S.]] | [[Category: Beese, L S.]] | ||
[[Category: Geacintov, N E.]] | [[Category: Geacintov, N E.]] | ||
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[[Category: Huang, X.]] | [[Category: Huang, X.]] | ||
[[Category: Luneva, N P.]] | [[Category: Luneva, N P.]] | ||
- | [[Category: | + | [[Category: Benzopyrene]] |
- | [[Category: | + | [[Category: Dna lesion]] |
- | + | [[Category: Dna polymerase i]] | |
- | [[Category: | + | [[Category: Dna replication]] |
- | [[Category: | + | [[Category: Klenow fragment]] |
- | [[Category: | + | [[Category: Translation replication]] |
- | [[Category: | + | ''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 | + |
Revision as of 11:50, 3 May 2008
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
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 Page seeded by OCA on Sat May 3 14:50:39 2008