2dpj
From Proteopedia
(New page: 200px<br /> <applet load="2dpj" size="450" color="white" frame="true" align="right" spinBox="true" caption="2dpj, resolution 2.30Å" /> '''structure of hPoli ...) |
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| - | [[Image:2dpj.gif|left|200px]]<br /> | + | [[Image:2dpj.gif|left|200px]]<br /><applet load="2dpj" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="2dpj" size=" | + | |
caption="2dpj, resolution 2.30Å" /> | caption="2dpj, resolution 2.30Å" /> | ||
'''structure of hPoli with DNA and dTTP'''<br /> | '''structure of hPoli with DNA and dTTP'''<br /> | ||
==Overview== | ==Overview== | ||
| - | The 1,N6-ethenodeoxyadenosine (epsilon dA) lesion is promutagenic and has | + | The 1,N6-ethenodeoxyadenosine (epsilon dA) lesion is promutagenic and has been implicated in carcinogenesis. We show here that human Pol iota, a Y-family DNA polymerase, can promote replication through this lesion by proficiently incorporating a nucleotide opposite it. The structural basis of this action is rotation of the epsilon dA adduct to the syn conformation in the Pol iota active site and presentation of its 'Hoogsteen edge' for hydrogen-bonding with incoming dTTP or dCTP. We also show that Pol zeta carries out the subsequent extension reaction and that efficiency of extension from epsilon dA x T is notably higher than from epsilon dA x C. Together, our studies reveal for the first time how the exocyclic epsilon dA adduct is accommodated in a DNA polymerase active site, and they show that the combined action of Pol iota and Pol zeta provides for efficient and error-free synthesis through this potentially carcinogenic DNA lesion. |
==About this Structure== | ==About this Structure== | ||
| - | 2DPJ is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with MG and TTP 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:// | + | 2DPJ is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=MG:'>MG</scene> and <scene name='pdbligand=TTP:'>TTP</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=2DPJ OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Aggarwal, A | + | [[Category: Aggarwal, A K.]] |
| - | [[Category: Johnson, R | + | [[Category: Johnson, R E.]] |
| - | [[Category: Nair, D | + | [[Category: Nair, D T.]] |
[[Category: Prakash, L.]] | [[Category: Prakash, L.]] | ||
[[Category: Prakash, S.]] | [[Category: Prakash, S.]] | ||
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[[Category: lesion bypass]] | [[Category: lesion bypass]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 17:01:11 2008'' |
Revision as of 15:01, 21 February 2008
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structure of hPoli with DNA and dTTP
Overview
The 1,N6-ethenodeoxyadenosine (epsilon dA) lesion is promutagenic and has been implicated in carcinogenesis. We show here that human Pol iota, a Y-family DNA polymerase, can promote replication through this lesion by proficiently incorporating a nucleotide opposite it. The structural basis of this action is rotation of the epsilon dA adduct to the syn conformation in the Pol iota active site and presentation of its 'Hoogsteen edge' for hydrogen-bonding with incoming dTTP or dCTP. We also show that Pol zeta carries out the subsequent extension reaction and that efficiency of extension from epsilon dA x T is notably higher than from epsilon dA x C. Together, our studies reveal for the first time how the exocyclic epsilon dA adduct is accommodated in a DNA polymerase active site, and they show that the combined action of Pol iota and Pol zeta provides for efficient and error-free synthesis through this potentially carcinogenic DNA lesion.
About this Structure
2DPJ 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
Hoogsteen base pair formation promotes synthesis opposite the 1,N6-ethenodeoxyadenosine lesion by human DNA polymerase iota., Nair DT, Johnson RE, Prakash L, Prakash S, Aggarwal AK, Nat Struct Mol Biol. 2006 Jul;13(7):619-25. Epub 2006 Jul 2. PMID:16819516
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