2dpi: Difference between revisions

Revision as of 18:01, 21 February 2008

Ternary complex of hPoli with DNA and dCTP

OverviewOverview

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 StructureAbout this Structure

2DPI 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.

ReferenceReference

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

Page seeded by OCA on Thu Feb 21 17:01:12 2008

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA

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-[[Image:2dpi.gif|left|200px]]<br />
+[[Image:2dpi.gif|left|200px]]<br /><applet load="2dpi" size="350" color="white" frame="true" align="right" spinBox="true"
-<applet load="2dpi" size="450" color="white" frame="true" align="right" spinBox="true"
 caption="2dpi, resolution 2.30&Aring;" />
 '''Ternary complex of hPoli with DNA and dCTP'''<br />
 ==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.
+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==
-DPI 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 DCP 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://ispc.weizmann.ac.il/oca-bin/ocashort?id=2DPI OCA].
+DPI 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=DCP:'>DCP</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=2DPI OCA].
 ==Reference==
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 [[Category: Homo sapiens]]
 [[Category: Single protein]]
-[[Category: Aggarwal, A.K.]]
+[[Category: Aggarwal, A K.]]
-[[Category: Johnson, R.E.]]
+[[Category: Johnson, R E.]]
-[[Category: Nair, D.T.]]
+[[Category: Nair, D T.]]
 [[Category: Prakash, L.]]
 [[Category: Prakash, S.]]
@@ Line 26: / Line 25: @@
 [[Category: lesion bypass]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 21:39:00 2007''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 17:01:12 2008''