View source for 4fbt


==Dpo4 post-insertion complex with the N-(deoxyguanosin-8-yl)-1-aminopyrene lesion==
<StructureSection load='4fbt' size='340' side='right' caption='[[4fbt]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4fbt]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Sulso Sulso]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4FBT OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4FBT 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=DGT:2-DEOXYGUANOSINE-5-TRIPHOSPHATE'>DGT</scene>, <scene name='pdbligand=GTP:GUANOSINE-5-TRIPHOSPHATE'>GTP</scene></td></tr>
<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=DG8:2-DEOXY-8-(PYREN-1-YLAMINO)GUANOSINE+5-(DIHYDROGEN+PHOSPHATE)'>DG8</scene></td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4fbu|4fbu]]</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=273057 SULSO])</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=4fbt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4fbt OCA], [http://pdbe.org/4fbt PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4fbt RCSB], [http://www.ebi.ac.uk/pdbsum/4fbt PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4fbt 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] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Polycyclic aromatic hydrocarbons and their nitro derivatives are culprits of the detrimental health effects of environmental pollution. These hydrophobic compounds metabolize to reactive species and attach to DNA producing bulky lesions, such as N-[deoxyguanosine-8-yl]-1-aminopyrene (APG), in genomic DNA. The bulky adducts block DNA replication by high-fidelity polymerases and compromise replication fidelities and efficiencies by specialized lesion bypass polymerases. Here we present three crystal structures of the DNA polymerase Dpo4, a model translesion DNA polymerase of the Y family, in complex with APG-lesion-containing DNA in pre-insertion and extension stages. APG is captured in two conformations in the pre-insertion complex; one is highly exposed to the solvent, whereas the other is harbored in a shallow cleft between the finger and unique Y family little finger domain. In contrast, APG is in a single conformation at the extension stage, in which the pyrene ring is sandwiched between the little finger domain and a base from the turning back single-stranded template strand. Strikingly, a nucleotide intercalates the DNA helix to form a quaternary complex with Dpo4, DNA, and an incoming nucleotide, which stabilizes the distorted DNA structure at the extension stage. The unique APG DNA conformations in Dpo4 inhibit DNA translocation through the polymerase active site for APG bypass. We also modeled an insertion complex that illustrates a solvent-exposed pyrene ring contributing to an unstable insertion state. The structural work combined with our lesion replication assays provides a novel structural mechanism on bypass of DNA adducts containing polycyclic aromatic hydrocarbon moieties.

Structural Mechanism of Replication Stalling on a Bulky Amino-Polycyclic Aromatic Hydrocarbon DNA Adduct by a Y Family DNA Polymerase.,Kirouac KN, Basu AK, Ling H J Mol Biol. 2013 Jul 20. pii: S0022-2836(13)00454-3. doi:, 10.1016/j.jmb.2013.07.020. PMID:23876706<ref>PMID:23876706</ref>

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

==See Also==
*[[DNA polymerase|DNA polymerase]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: DNA-directed DNA polymerase]]
[[Category: Sulso]]
[[Category: Kirouac, K]]
[[Category: Ling, H]]
[[Category: Dna polymerase]]
[[Category: Transferase-dna complex]]