2hvh: Difference between revisions
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[[Image:2hvh.gif|left|200px]] | [[Image:2hvh.gif|left|200px]] | ||
'''ddCTP:O6MeG pair in the polymerase active site (0 position)''' | {{Structure | ||
|PDB= 2hvh |SIZE=350|CAPTION= <scene name='initialview01'>2hvh</scene>, resolution 2.492Å | |||
|SITE= | |||
|LIGAND= <scene name='pdbligand=SUC:SUCROSE'>SUC</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene> and <scene name='pdbligand=DCT:2',3'-DIDEOXYCYTIDINE 5'-TRIPHOSPHATE'>DCT</scene> | |||
|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] | |||
|GENE= polA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1422 Geobacillus stearothermophilus]) | |||
}} | |||
'''ddCTP:O6MeG pair in the polymerase active site (0 position)''' | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
2HVH is a [ | 2HVH is a [[Single protein]] structure of sequence 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=2HVH OCA]. | ||
==Reference== | ==Reference== | ||
The structural basis for the mutagenicity of O(6)-methyl-guanine lesions., Warren JJ, Forsberg LJ, Beese LS, Proc Natl Acad Sci U S A. 2006 Dec 26;103(52):19701-6. Epub 2006 Dec 18. PMID:[http:// | The structural basis for the mutagenicity of O(6)-methyl-guanine lesions., Warren JJ, Forsberg LJ, Beese LS, Proc Natl Acad Sci U S A. 2006 Dec 26;103(52):19701-6. Epub 2006 Dec 18. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/17179038 17179038] | ||
[[Category: DNA-directed DNA polymerase]] | [[Category: DNA-directed DNA polymerase]] | ||
[[Category: Geobacillus stearothermophilus]] | [[Category: Geobacillus stearothermophilus]] | ||
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[[Category: protein-dna complex]] | [[Category: protein-dna complex]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 17:22:03 2008'' | ||
Revision as of 18:22, 20 March 2008
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| , resolution 2.492Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | , , and | ||||||
| Gene: | polA (Geobacillus stearothermophilus) | ||||||
| Activity: | DNA-directed DNA polymerase, with EC number 2.7.7.7 | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
ddCTP:O6MeG pair in the polymerase active site (0 position)
OverviewOverview
Methylating agents are widespread environmental carcinogens that generate a broad spectrum of DNA damage. Methylation at the guanine O(6) position confers the greatest mutagenic and carcinogenic potential. DNA polymerases insert cytosine and thymine with similar efficiency opposite O(6)-methyl-guanine (O6MeG). We combined pre-steady-state kinetic analysis and a series of nine x-ray crystal structures to contrast the reaction pathways of accurate and mutagenic replication of O6MeG in a high-fidelity DNA polymerase from Bacillus stearothermophilus. Polymerases achieve substrate specificity by selecting for nucleotides with shape and hydrogen-bonding patterns that complement a canonical DNA template. Our structures reveal that both thymine and cytosine O6MeG base pairs evade proofreading by mimicking the essential molecular features of canonical substrates. The steric mimicry depends on stabilization of a rare cytosine tautomer in C.O6MeG-polymerase complexes. An unusual electrostatic interaction between O-methyl protons and a thymine carbonyl oxygen helps stabilize T.O6MeG pairs bound to DNA polymerase. Because DNA methylators constitute an important class of chemotherapeutic agents, the molecular mechanisms of replication of these DNA lesions are important for our understanding of both the genesis and treatment of cancer.
About this StructureAbout this Structure
2HVH is a Single protein structure of sequence from Geobacillus stearothermophilus. Full crystallographic information is available from OCA.
ReferenceReference
The structural basis for the mutagenicity of O(6)-methyl-guanine lesions., Warren JJ, Forsberg LJ, Beese LS, Proc Natl Acad Sci U S A. 2006 Dec 26;103(52):19701-6. Epub 2006 Dec 18. PMID:17179038
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