3m9n: Difference between revisions

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[[Image:3m9n.png|left|200px]]
==Crystal Structure of Dpo4 in complex with DNA containing the major cisplatin lesion==
<StructureSection load='3m9n' size='340' side='right' caption='[[3m9n]], [[Resolution|resolution]] 1.93&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[3m9n]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Sulfolobus_solfataricus Sulfolobus solfataricus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3M9N OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3M9N FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=CPT:CISPLATIN'>CPT</scene>, <scene name='pdbligand=CTP:CYTIDINE-5-TRIPHOSPHATE'>CTP</scene></td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3m9m|3m9m]], [[3m9o|3m9o]]</td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">dbh, dpo4, SSO2448 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=2287 Sulfolobus solfataricus])</td></tr>
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[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] </span></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3m9n FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3m9n OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3m9n RCSB], [http://www.ebi.ac.uk/pdbsum/3m9n PDBsum]</span></td></tr>
</table>
== 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/m9/3m9n_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/chain_selection.php?pdb_ID=2ata ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Y-family DNA polymerases bypass Pt-GG, the cisplatin-DNA double-base lesion, contributing to the cisplatin resistance in tumour cells. To reveal the mechanism, we determined three structures of the Y-family DNA polymerase, Dpo4, in complex with Pt-GG DNA. The crystallographic snapshots show three stages of lesion bypass: the nucleotide insertions opposite the 3'G (first insertion) and 5'G (second insertion) of Pt-GG, and the primer extension beyond the lesion site. We observed a dynamic process, in which the lesion was converted from an open and angular conformation at the first insertion to a depressed and nearly parallel conformation at the subsequent reaction stages to fit into the active site of Dpo4. The DNA translocation-coupled conformational change may account for additional inhibition on the second insertion reaction. The structures illustrate that Pt-GG disturbs the replicating base pair in the active site, which reduces the catalytic efficiency and fidelity. The in vivo relevance of Dpo4-mediated Pt-GG bypass was addressed by a dpo-4 knockout strain of Sulfolobus solfataricus, which exhibits enhanced sensitivity to cisplatin and proteomic alterations consistent with genomic stress.


{{STRUCTURE_3m9n|  PDB=3m9n  |  SCENE=  }}
Structural insight into dynamic bypass of the major cisplatin-DNA adduct by Y-family polymerase Dpo4.,Wong JH, Brown JA, Suo Z, Blum P, Nohmi T, Ling H EMBO J. 2010 Jun 16;29(12):2059-69. Epub 2010 May 28. PMID:20512114<ref>PMID:20512114</ref>


===Crystal Structure of Dpo4 in complex with DNA containing the major cisplatin lesion===
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 
</div>
{{ABSTRACT_PUBMED_20512114}}
 
==About this Structure==
[[3m9n]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Sulfolobus_solfataricus Sulfolobus solfataricus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3M9N OCA].


==See Also==
==See Also==
*[[DNA polymerase|DNA polymerase]]
*[[DNA polymerase|DNA polymerase]]
 
== References ==
==Reference==
<references/>
<ref group="xtra">PMID:020512114</ref><references group="xtra"/>
__TOC__
</StructureSection>
[[Category: DNA-directed DNA polymerase]]
[[Category: DNA-directed DNA polymerase]]
[[Category: Sulfolobus solfataricus]]
[[Category: Sulfolobus solfataricus]]
[[Category: Ling, H.]]
[[Category: Ling, H]]
[[Category: Wong, J H.Y.]]
[[Category: Wong, J H.Y]]
[[Category: Cisplatin]]
[[Category: Cisplatin]]
[[Category: Dna]]
[[Category: Dna]]
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