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[[Image:2asl.gif|left|200px]]<br /><applet load="2asl" size="350" color="white" frame="true" align="right" spinBox="true"
caption="2asl, resolution 2.65&Aring;" />
'''oxoG-modified Postinsertion Binary Complex'''<br />


==Overview==
==oxoG-modified Postinsertion Binary Complex==
7,8-dihydro-8-oxoguanine (oxoG), the predominant lesion formed following oxidative damage of DNA by reactive oxygen species, is processed differently by replicative and bypass polymerases. Our kinetic primer extension studies demonstrate that the bypass polymerase Dpo4 preferentially inserts C opposite oxoG, and also preferentially extends from the oxoG*C base pair, thus achieving error-free bypass of this lesion. We have determined the crystal structures of preinsertion binary, insertion ternary, and postinsertion binary complexes of oxoG-modified template-primer DNA and Dpo4. These structures provide insights into the translocation mechanics of the bypass polymerase during a complete cycle of nucleotide incorporation. Specifically, during noncovalent dCTP insertion opposite oxoG (or G), the little-finger domain-DNA phosphate contacts translocate by one nucleotide step, while the thumb domain-DNA phosphate contacts remain fixed. By contrast, during the nucleotidyl transfer reaction that covalently incorporates C opposite oxoG, the thumb-domain-phosphate contacts are translocated by one nucleotide step, while the little-finger contacts with phosphate groups remain fixed. These stepwise conformational transitions accompanying nucleoside triphosphate binding and covalent nucleobase incorporation during a full replication cycle of Dpo4-catalyzed bypass of the oxoG lesion are distinct from the translocation events in replicative polymerases.
<StructureSection load='2asl' size='340' side='right'caption='[[2asl]], [[Resolution|resolution]] 2.65&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2asl]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Saccharolobus_solfataricus Saccharolobus solfataricus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2ASL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2ASL 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]] 2.65&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=8OG:8-OXO-2-DEOXY-GUANOSINE-5-MONOPHOSPHATE'>8OG</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=DOC:2,3-DIDEOXYCYTIDINE-5-MONOPHOSPHATE'>DOC</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=2asl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2asl OCA], [https://pdbe.org/2asl PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2asl RCSB], [https://www.ebi.ac.uk/pdbsum/2asl PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2asl ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/DPO4_SACS2 DPO4_SACS2] Poorly processive, error-prone DNA polymerase involved in untargeted mutagenesis. Copies undamaged DNA at stalled replication forks, which arise in vivo from mismatched or misaligned primer ends. These misaligned primers can be extended by PolIV. Exhibits no 3'-5' exonuclease (proofreading) activity. It is involved in translesional synthesis.
== 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/as/2asl_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=2asl ConSurf].
<div style="clear:both"></div>


==About this Structure==
==See Also==
2ASL is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Sulfolobus_solfataricus Sulfolobus solfataricus] with <scene name='pdbligand=CA:'>CA</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. 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=2ASL OCA].
*[[DNA polymerase 3D structures|DNA polymerase 3D structures]]
 
__TOC__
==Reference==
</StructureSection>
Stepwise translocation of Dpo4 polymerase during error-free bypass of an oxoG lesion., Rechkoblit O, Malinina L, Cheng Y, Kuryavyi V, Broyde S, Geacintov NE, Patel DJ, PLoS Biol. 2006 Jan;4(1):e11. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=16379496 16379496]
[[Category: Large Structures]]
[[Category: DNA-directed DNA polymerase]]
[[Category: Saccharolobus solfataricus]]
[[Category: Single protein]]
[[Category: Broyde S]]
[[Category: Sulfolobus solfataricus]]
[[Category: Cheng Y]]
[[Category: Broyde, S.]]
[[Category: Geacintov NE]]
[[Category: Cheng, Y.]]
[[Category: Kuryavyi V]]
[[Category: Geacintov, N E.]]
[[Category: Malinina L]]
[[Category: Kuryavyi, V.]]
[[Category: Patel DJ]]
[[Category: Malinina, L.]]
[[Category: Rechkoblit O]]
[[Category: Patel, D J.]]
[[Category: Rechkoblit, O.]]
[[Category: CA]]
[[Category: 8-oxoguanine]]
[[Category: dna polymerase]]
[[Category: lesion bypass]]
[[Category: y-family]]
 
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:30:33 2008''

Latest revision as of 12:14, 14 February 2024

oxoG-modified Postinsertion Binary ComplexoxoG-modified Postinsertion Binary Complex

Structural highlights

2asl is a 6 chain structure with sequence from Saccharolobus solfataricus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.65Å
Ligands:, ,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

DPO4_SACS2 Poorly processive, error-prone DNA polymerase involved in untargeted mutagenesis. Copies undamaged DNA at stalled replication forks, which arise in vivo from mismatched or misaligned primer ends. These misaligned primers can be extended by PolIV. Exhibits no 3'-5' exonuclease (proofreading) activity. It is involved in translesional synthesis.

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

See Also

2asl, resolution 2.65Å

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