View source for 4qwc


==Ternary Crystal Structures of a Y-family DNA polymerase DPO4 from Sulfobus Solfataricus in Comples with DNA and L-DCDP==
<StructureSection load='4qwc' size='340' side='right'caption='[[4qwc]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4qwc]] 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=4QWC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4QWC 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]] 2.4&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=DOC:2,3-DIDEOXYCYTIDINE-5-MONOPHOSPHATE'>DOC</scene>, <scene name='pdbligand=LTP:4-AMINO-1-{2-DEOXY-5-O-[(R)-HYDROXY(PHOSPHONOOXY)PHOSPHORYL]-BETA-L-ERYTHRO-PENTOFURANOSYL}PYRIMIDIN-2(1H)-ONE'>LTP</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=4qwc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4qwc OCA], [https://pdbe.org/4qwc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4qwc RCSB], [https://www.ebi.ac.uk/pdbsum/4qwc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4qwc 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.
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== Publication Abstract from PubMed ==
Considering that all natural nucleotides (D-dNTPs) and the building blocks (D-dNMPs) of DNA chains possess D-stereochemistry, DNA polymerases and reverse transcriptases (RTs) likely possess strongD-stereoselectivity by preferably binding and incorporating D-dNTPs over unnatural L-dNTPs during DNA synthesis. Surprisingly, a structural basis for the discrimination against L-dNTPs by DNA polymerases or RTs has not been established although L-deoxycytidine analogs (lamivudine and emtricitabine) and L-thymidine (telbivudine) have been widely used as antiviral drugs for years. Here we report seven high-resolution ternary crystal structures of a prototype Y-family DNA polymerase, DNA, and D-dCTP, D-dCDP, L-dCDP, or the diphosphates and triphosphates of lamivudine and emtricitabine. These structures reveal that relative to D-dCTP, each of these L-nucleotides has its sugar ring rotated by 180 degrees with an unusual O4'-endo sugar puckering and exhibits multiple triphosphate-binding conformations within the active site of the polymerase. Such rare binding modes significantly decrease the incorporation rates and efficiencies of these L-nucleotides catalyzed by the polymerase.

Structural and kinetic insights into binding and incorporation of L-nucleotide analogs by a Y-family DNA polymerase.,Gaur V, Vyas R, Fowler JD, Efthimiopoulos G, Feng JY, Suo Z Nucleic Acids Res. 2014 Aug 7. pii: gku709. PMID:25104018<ref>PMID:25104018</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4qwc" style="background-color:#fffaf0;"></div>

==See Also==
*[[DNA polymerase 3D structures|DNA polymerase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Saccharolobus solfataricus P2]]
[[Category: Synthetic construct]]
[[Category: Suo Z]]
[[Category: Vyas R]]