1mq3: Difference between revisions
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==Overview== | ==Overview== | ||
Oxidative damage to DNA generates 8-oxo-7,8-dihydro-2'-deoxyguanosine | Oxidative damage to DNA generates 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG). During DNA replication and repair synthesis, 8-oxodG can pair with cytosine or adenine. The ability to accurately replicate through this lesion depends on the DNA polymerase. We report the first structure of a polymerase with a promutagenic DNA lesion, 8-oxodG, in the confines of its active site. The modified guanine residue is in an anti conformation and forms Watson-Crick hydrogen bonds with an incoming dCTP. To accommodate the oxygen at C8, the 5'-phosphate backbone of the templating nucleotide flips 180 degrees. Thus, the flexibility of the template sugar-phosphate backbone near the polymerase active site is one parameter that influences the anti-syn equilibrium of 8-oxodG. Our results provide insights into the mechanisms employed by polymerases to select the complementary dNTP. | ||
==About this Structure== | ==About this Structure== | ||
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[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Beard, W | [[Category: Beard, W A.]] | ||
[[Category: Grollman, A | [[Category: Grollman, A P.]] | ||
[[Category: Krahn, J | [[Category: Krahn, J M.]] | ||
[[Category: Miller, H.]] | [[Category: Miller, H.]] | ||
[[Category: Wilson, S | [[Category: Wilson, S H.]] | ||
[[Category: DCP]] | [[Category: DCP]] | ||
[[Category: MG]] | [[Category: MG]] | ||
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[[Category: transferase]] | [[Category: transferase]] | ||
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Revision as of 11:57, 21 February 2008
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Human DNA Polymerase Beta Complexed With Gapped DNA Containing an 8-oxo-7,8-dihydro-Guanine Template Paired with dCTP
Overview
Oxidative damage to DNA generates 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG). During DNA replication and repair synthesis, 8-oxodG can pair with cytosine or adenine. The ability to accurately replicate through this lesion depends on the DNA polymerase. We report the first structure of a polymerase with a promutagenic DNA lesion, 8-oxodG, in the confines of its active site. The modified guanine residue is in an anti conformation and forms Watson-Crick hydrogen bonds with an incoming dCTP. To accommodate the oxygen at C8, the 5'-phosphate backbone of the templating nucleotide flips 180 degrees. Thus, the flexibility of the template sugar-phosphate backbone near the polymerase active site is one parameter that influences the anti-syn equilibrium of 8-oxodG. Our results provide insights into the mechanisms employed by polymerases to select the complementary dNTP.
About this Structure
1MQ3 is a Single protein structure of sequence from Homo sapiens with MG, NA and DCP 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 DNA polymerase beta with the mutagenic DNA lesion 8-oxodeoxyguanine reveals structural insights into its coding potential., Krahn JM, Beard WA, Miller H, Grollman AP, Wilson SH, Structure. 2003 Jan;11(1):121-7. PMID:12517346
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