2alz: Difference between revisions

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New page: left|200px<br /> <applet load="2alz" size="450" color="white" frame="true" align="right" spinBox="true" caption="2alz, resolution 2.50Å" /> '''Ternary Complex of ...
 
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[[Image:2alz.gif|left|200px]]<br />
<applet load="2alz" size="450" color="white" frame="true" align="right" spinBox="true"
caption="2alz, resolution 2.50&Aring;" />
'''Ternary Complex of hPoli with DNA and dCTP'''<br />


==Overview==
==Ternary Complex of hPoli with DNA and dCTP==
Human DNA polymerase iota (hPoliota), a member of the Y family of DNA, polymerases, differs in remarkable ways from other DNA polymerases, incorporating correct nucleotides opposite template purines with a much, higher efficiency and fidelity than opposite template pyrimidines. We, present here the crystal structure of hPoliota bound to template G and, incoming dCTP, which reveals a G.C + Hoogsteen base pair in a DNA, polymerase active site. We show that the hPoliota active site has evolved, to favor Hoogsteen base pairing, wherein the template sugar is fixed in a, cavity that reduces the C1'-C1' distance across the nascent base pair from, approximately 10.5 A in other DNA polymerases to 8.6 A in hPoliota. The, rotation of G from anti to syn is then largely in response to this, curtailed C1'-C1' distance. A G.C+ Hoogsteen base pair suggests a specific, mechanism for hPoliota's ability to bypass N(2)-adducted guanines that, obstruct replication.
<StructureSection load='2alz' size='340' side='right'caption='[[2alz]], [[Resolution|resolution]] 2.50&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2alz]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2ALZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2ALZ FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.5&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DCP:2-DEOXYCYTIDINE-5-TRIPHOSPHATE'>DCP</scene>, <scene name='pdbligand=DOC:2,3-DIDEOXYCYTIDINE-5-MONOPHOSPHATE'>DOC</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2alz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2alz OCA], [https://pdbe.org/2alz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2alz RCSB], [https://www.ebi.ac.uk/pdbsum/2alz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2alz ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/POLI_HUMAN POLI_HUMAN] Error-prone DNA polymerase specifically involved in DNA repair. Plays an important role in translesion synthesis, where the normal high-fidelity DNA polymerases cannot proceed and DNA synthesis stalls. Favors Hoogsteen base-pairing in the active site. Inserts the correct base with high-fidelity opposite an adenosine template. Exhibits low fidelity and efficiency opposite a thymidine template, where it will preferentially insert guanosine. May play a role in hypermutation of immunogobulin genes. Forms a Schiff base with 5'-deoxyribose phosphate at abasic sites, but may not have lyase activity.<ref>PMID:11013228</ref> <ref>PMID:11251121</ref> <ref>PMID:11387224</ref> <ref>PMID:12410315</ref> <ref>PMID:14630940</ref> <ref>PMID:15199127</ref> <ref>PMID:15254543</ref>
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/al/2alz_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2alz ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Human DNA polymerase iota (hPoliota), a member of the Y family of DNA polymerases, differs in remarkable ways from other DNA polymerases, incorporating correct nucleotides opposite template purines with a much higher efficiency and fidelity than opposite template pyrimidines. We present here the crystal structure of hPoliota bound to template G and incoming dCTP, which reveals a G.C + Hoogsteen base pair in a DNA polymerase active site. We show that the hPoliota active site has evolved to favor Hoogsteen base pairing, wherein the template sugar is fixed in a cavity that reduces the C1'-C1' distance across the nascent base pair from approximately 10.5 A in other DNA polymerases to 8.6 A in hPoliota. The rotation of G from anti to syn is then largely in response to this curtailed C1'-C1' distance. A G.C+ Hoogsteen base pair suggests a specific mechanism for hPoliota's ability to bypass N(2)-adducted guanines that obstruct replication.


==About this Structure==
Human DNA polymerase iota incorporates dCTP opposite template G via a G.C + Hoogsteen base pair.,Nair DT, Johnson RE, Prakash L, Prakash S, Aggarwal AK Structure. 2005 Oct;13(10):1569-77. PMID:16216587<ref>PMID:16216587</ref>
2ALZ 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=2ALZ OCA].


==Reference==
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
Human DNA polymerase iota incorporates dCTP opposite template G via a G.C + Hoogsteen base pair., Nair DT, Johnson RE, Prakash L, Prakash S, Aggarwal AK, Structure. 2005 Oct;13(10):1569-77. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=16216587 16216587]
</div>
[[Category: DNA-directed DNA polymerase]]
<div class="pdbe-citations 2alz" style="background-color:#fffaf0;"></div>
 
==See Also==
*[[DNA polymerase 3D structures|DNA polymerase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Single protein]]
[[Category: Large Structures]]
[[Category: Aggarwal, A.K.]]
[[Category: Aggarwal AK]]
[[Category: Johnson, R.E.]]
[[Category: Johnson RE]]
[[Category: Nair, D.T.]]
[[Category: Nair DT]]
[[Category: Prakash, L.]]
[[Category: Prakash L]]
[[Category: Prakash, S.]]
[[Category: Prakash S]]
[[Category: DCP]]
[[Category: MG]]
[[Category: dna polymerase]]
[[Category: hoogsteen base pair]]
[[Category: right handed]]
[[Category: template g. incoming dctp]]
[[Category: ternary complex]]
 
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