1xc9

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[[Image:1xc9.gif|left|200px]]<br /><applet load="1xc9" size="350" color="white" frame="true" align="right" spinBox="true"
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[[Image:1xc9.gif|left|200px]]
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caption="1xc9, resolution 1.90&Aring;" />
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'''Structure of a high-fidelity polymerase bound to a benzo[a]pyrene adduct that blocks replication'''<br />
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{{Structure
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|PDB= 1xc9 |SIZE=350|CAPTION= <scene name='initialview01'>1xc9</scene>, resolution 1.90&Aring;
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|SITE=
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|LIGAND= <scene name='pdbligand=SUC:SUCROSE'>SUC</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene> and <scene name='pdbligand=BAP:1,2,3-TRIHYDROXY-1,2,3,4-TETRAHYDROBENZO[A]PYRENE'>BAP</scene>
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|ACTIVITY= [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]
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|GENE=
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}}
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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==
==Overview==
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==About this Structure==
==About this Structure==
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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].
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1XC9 is a [[Protein complex]] structure of sequences from [http://en.wikipedia.org/wiki/Geobacillus_stearothermophilus Geobacillus stearothermophilus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1XC9 OCA].
==Reference==
==Reference==
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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://ispc.weizmann.ac.il//pmbin/getpm?pmid=15548515 15548515]
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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: Geobacillus stearothermophilus]]
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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]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:53:16 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 15:07:53 2008''

Revision as of 13:07, 20 March 2008


PDB ID 1xc9

Drag the structure with the mouse to rotate
, resolution 1.90Å
Ligands: , , and
Activity: DNA-directed DNA polymerase, with EC number 2.7.7.7
Coordinates: save as pdb, mmCIF, xml



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. 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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