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4tqs

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Ternary complex of Y-family DNA polymerase Dpo4 with (5'S)-8,5'-Cyclo-2'-deoxyguanosine and dCTP

Structural highlights

4tqs is a 6 chain structure with sequence from Saccharolobus solfataricus P2 and Synthetic construct. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.06Å
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.

Publication Abstract from PubMed

The (5'S)-8,5'-cyclo-2'-deoxyguanosine (S-cdG) lesion is produced from reactions of DNA with hydroxyl radicals generated from ionizing radiation or endogenous oxidative metabolisms. An elevated level of S-cdG has been detected in Xeroderma pigmentosum, Cockayne syndrome, breast cancer patients, and aged mice. S-dG blocks DNA replication and transcription in vitro and in human cells and produces mutant replication and transcription products in vitro and in vivo. Major cellular protection against S-dG includes nucleotide excision repair and translesion DNA synthesis. We used kinetic and crystallographic approaches to elucidate the molecular mechanisms of S-cdG-induced DNA replication stalling using model B-family Sulfolobus solfataricus P2 DNA polymerase B1 (Dpo1) and Y-family S. solfataricus P2 DNA polymerase IV (Dpo4). Dpo1 and Dpo4 inefficiently bypassed S-cdG with dCTP preferably incorporated and dTTP (for Dpo4) or dATP (for Dpo1) misincorporated. Pre-steady-state kinetics and crystallographic data mechanistically explained the low-efficiency bypass. For Dpo1, S-cdG attenuated Kd,dNTP,app and kpol. For Dpo4, the S-cdG-adducted duplex caused a 6-fold decrease in Dpo4:DNA binding affinity and significantly reduced the concentration of the productive Dpo4:DNA:dCTP complex. Consistent with the inefficient bypass, crystal structures of Dpo4:DNA(S-cdG):dCTP (error-free) and Dpo4:DNA(S-cdG):dTTP (error-prone) complexes were catalytically incompetent. In the Dpo4:DNA(S-cdG):dTTP structure, S-cdG induced a loop structure and caused an unusual 5'-template base clustering at the active site, providing the first structural evidence of the previously suggested template loop structure that can be induced by a cyclopurine lesion. Together, our results provided mechanistic insights into S-cdG-induced DNA replication stalling.

Kinetic and Structural Mechanisms of (5'S)-8,5'-Cyclo-2'-deoxyguanosine-Induced DNA Replication Stalling.,Xu W, Ouellette AM, Wawrzak Z, Shriver SJ, Anderson SM, Zhao L Biochemistry. 2015 Jan 13. PMID:25569151^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Xu W, Ouellette AM, Wawrzak Z, Shriver SJ, Anderson SM, Zhao L. Kinetic and Structural Mechanisms of (5'S)-8,5'-Cyclo-2'-deoxyguanosine-Induced DNA Replication Stalling. Biochemistry. 2015 Jan 13. PMID:25569151 doi:http://dx.doi.org/10.1021/bi5014936

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4tqs"

Categories: Large Structures | Saccharolobus solfataricus P2 | Synthetic construct | Zhao L

@@ Line 1: / Line 1: @@
 ==Ternary complex of Y-family DNA polymerase Dpo4 with (5'S)-8,5'-Cyclo-2'-deoxyguanosine and dCTP==
-<StructureSection load='4tqs' size='340' side='right' caption='[[4tqs]], [[Resolution|resolution]] 2.06&Aring;' scene=''>
+<StructureSection load='4tqs' size='340' side='right'caption='[[4tqs]], [[Resolution|resolution]] 2.06&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[4tqs]] is a 6 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4TQS OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4TQS FirstGlance]. <br>
+<table><tr><td colspan='2'>[[4tqs]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Saccharolobus_solfataricus_P2 Saccharolobus solfataricus P2] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4TQS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4TQS FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><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>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.06&#8491;</td></tr>
-<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=2LF:(6S,7S,8S,10R)-2-AMINO-8-HYDROXY-4-OXO-3,6,7,8,9,10-HEXAHYDRO-4H-7,10-EPOXYAZEPINO[1,2-E]PURIN-6-YL+DIHYDROGEN+PHOSPHATE'>2LF</scene></td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=2LF:(6S,7S,8S,10R)-2-AMINO-8-HYDROXY-4-OXO-3,6,7,8,9,10-HEXAHYDRO-4H-7,10-EPOXYAZEPINO[1,2-E]PURIN-6-YL+DIHYDROGEN+PHOSPHATE'>2LF</scene>, <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='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'>[https://proteopedia.org/fgij/fg.htm?mol=4tqs FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4tqs OCA], [https://pdbe.org/4tqs PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4tqs RCSB], [https://www.ebi.ac.uk/pdbsum/4tqs PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4tqs ProSAT]</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=4tqs FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4tqs OCA], [http://pdbe.org/4tqs PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4tqs RCSB], [http://www.ebi.ac.uk/pdbsum/4tqs PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4tqs ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[http://www.uniprot.org/uniprot/DPO4_SULSO DPO4_SULSO]] 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.[HAMAP-Rule:MF_01113]
+[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.
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 22: / Line 21: @@
 ==See Also==
-*[[DNA polymerase|DNA polymerase]]
+*[[DNA polymerase 3D structures|DNA polymerase 3D structures]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
-[[Category: DNA-directed DNA polymerase]]
+[[Category: Large Structures]]
-[[Category: Zhao, L]]
+[[Category: Saccharolobus solfataricus P2]]
-[[Category: Cyclopurine]]
+[[Category: Synthetic construct]]
-[[Category: Dna damage]]
+[[Category: Zhao L]]
-[[Category: Transferase]]
-[[Category: Translesion dna synthesis]]
-[[Category: Y-family dna polymerase]]

4tqs

From Proteopedia

Current revision

Ternary complex of Y-family DNA polymerase Dpo4 with (5'S)-8,5'-Cyclo-2'-deoxyguanosine and dCTP

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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