1xc9
From Proteopedia
(New page: 200px<br /><applet load="1xc9" size="450" color="white" frame="true" align="right" spinBox="true" caption="1xc9, resolution 1.90Å" /> '''Structure of a high-...) |
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| - | [[Image:1xc9.gif|left|200px]]<br /><applet load="1xc9" size=" | + | [[Image:1xc9.gif|left|200px]]<br /><applet load="1xc9" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1xc9, resolution 1.90Å" /> | caption="1xc9, resolution 1.90Å" /> | ||
'''Structure of a high-fidelity polymerase bound to a benzo[a]pyrene adduct that blocks replication'''<br /> | '''Structure of a high-fidelity polymerase bound to a benzo[a]pyrene adduct that blocks replication'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Of the carcinogens to which humans are most frequently exposed, the | + | 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== | ==About this Structure== | ||
| - | 1XC9 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Geobacillus_stearothermophilus Geobacillus stearothermophilus] with SUC, SO4, MG and BAP as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/DNA-directed_DNA_polymerase DNA-directed DNA polymerase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.7.7 2.7.7.7] Full crystallographic information is available from [http:// | + | 1XC9 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Geobacillus_stearothermophilus Geobacillus stearothermophilus] with <scene name='pdbligand=SUC:'>SUC</scene>, <scene name='pdbligand=SO4:'>SO4</scene>, <scene name='pdbligand=MG:'>MG</scene> and <scene name='pdbligand=BAP:'>BAP</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/DNA-directed_DNA_polymerase DNA-directed DNA polymerase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.7.7 2.7.7.7] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1XC9 OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Geobacillus stearothermophilus]] | [[Category: Geobacillus stearothermophilus]] | ||
[[Category: Protein complex]] | [[Category: Protein complex]] | ||
| - | [[Category: Beese, L | + | [[Category: Beese, L S.]] |
| - | [[Category: Geacintov, N | + | [[Category: Geacintov, N E.]] |
| - | [[Category: Hsu, G | + | [[Category: Hsu, G W.]] |
[[Category: Huang, X.]] | [[Category: Huang, X.]] | ||
| - | [[Category: Luneva, N | + | [[Category: Luneva, N P.]] |
[[Category: BAP]] | [[Category: BAP]] | ||
[[Category: MG]] | [[Category: MG]] | ||
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[[Category: dna polymerase i; dna replication; klenow fragment; benzo[a]pyrene; benzopyrene; dna lesion; translation replication]] | [[Category: dna polymerase i; dna replication; klenow fragment; benzo[a]pyrene; benzopyrene; dna lesion; translation replication]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:53:16 2008'' |
Revision as of 13:53, 21 February 2008
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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 , , and 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]]
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