1mq3

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==Overview==
==Overview==
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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.
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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]]
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[[Category: Beard, W.A.]]
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[[Category: Beard, W A.]]
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[[Category: Grollman, A.P.]]
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[[Category: Grollman, A P.]]
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[[Category: Krahn, J.M.]]
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[[Category: Krahn, J M.]]
[[Category: Miller, H.]]
[[Category: Miller, H.]]
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[[Category: Wilson, S.H.]]
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[[Category: Wilson, S H.]]
[[Category: DCP]]
[[Category: DCP]]
[[Category: MG]]
[[Category: MG]]
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[[Category: transferase]]
[[Category: transferase]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri Feb 15 16:25:13 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:57:53 2008''

Revision as of 11:57, 21 February 2008


1mq3, resolution 2.8Å

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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 , 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 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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