3tae: Difference between revisions
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<StructureSection load='3tae' size='340' side='right'caption='[[3tae]], [[Resolution|resolution]] 2.71Å' scene=''> | <StructureSection load='3tae' size='340' side='right'caption='[[3tae]], [[Resolution|resolution]] 2.71Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[3tae]] is a 12 chain structure with sequence from [ | <table><tr><td colspan='2'>[[3tae]] is a 12 chain structure with sequence from [https://en.wikipedia.org/wiki/Bpr69 Bpr69]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3TAE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3TAE FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> | ||
<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=5OC:2-DEOXY-5-HYDROXYCYTIDINE+5-(DIHYDROGEN+PHOSPHATE)'>5OC</scene></td></tr> | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=5OC:2-DEOXY-5-HYDROXYCYTIDINE+5-(DIHYDROGEN+PHOSPHATE)'>5OC</scene></td></tr> | ||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3tab|3tab]], [[3taf|3taf]], [[3tag|3tag]]</td></tr> | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3tab|3tab]], [[3taf|3taf]], [[3tag|3tag]]</div></td></tr> | ||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">43, gp43 ([ | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">43, gp43 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=12353 BPR69])</td></tr> | ||
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[ | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/DNA-directed_DNA_polymerase DNA-directed DNA polymerase], with EC number [https://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'>[ | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3tae FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3tae OCA], [https://pdbe.org/3tae PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3tae RCSB], [https://www.ebi.ac.uk/pdbsum/3tae PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3tae ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
[[ | [[https://www.uniprot.org/uniprot/DPOL_BPR69 DPOL_BPR69]] This polymerase possesses two enzymatic activities: DNA synthesis (polymerase) and an exonucleolytic activity that degrades single stranded DNA in the 3'- to 5'-direction. | ||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
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</div> | </div> | ||
<div class="pdbe-citations 3tae" style="background-color:#fffaf0;"></div> | <div class="pdbe-citations 3tae" style="background-color:#fffaf0;"></div> | ||
== References == | == References == | ||
<references/> | <references/> | ||
Revision as of 19:49, 6 July 2022
5-hydroxycytosine paired with dAMP in RB69 gp435-hydroxycytosine paired with dAMP in RB69 gp43
Structural highlights
Function[DPOL_BPR69] This polymerase possesses two enzymatic activities: DNA synthesis (polymerase) and an exonucleolytic activity that degrades single stranded DNA in the 3'- to 5'-direction. Publication Abstract from PubMed5-Hydroxycytosine (5-OHC) is a stable oxidation product of cytosine associated with an increased frequency of C --> T transition mutations. When this lesion escapes recognition by the base excision repair pathway and persists to serve as a templating base during DNA synthesis, replicative DNA polymerases often misincorporate dAMP at the primer terminus, which can lead to fixation of mutations and subsequent disease. To characterize the dynamics of DNA synthesis opposite 5-OHC, we initiated a comparison of unmodified dCMP to 5-OHC, 5-fluorocytosine (5-FC), and 5-methylcytosine (5-MEC) in which these bases act as templates in the active site of RB69 gp43, a high-fidelity DNA polymerase sharing homology with human replicative DNA polymerases. This study presents the first crystal structure of any DNA polymerase binding this physiologically important premutagenic DNA lesion, showing that while dGMP is stabilized by 5-OHC through normal Watson-Crick base pairing, incorporation of dAMP leads to unstacking and instability in the template. Furthermore, the electronegativity of the C5 substituent appears to be important in the miscoding potential of these cytosine-like templates. While dAMP is incorporated opposite 5-OHC approximately 5 times more efficiently than opposite unmodified dCMP, an elevated level of incorporation is also observed opposite 5-FC but not 5-MEC. Taken together, these data imply that the nonuniform templating by 5-OHC is due to weakened stacking capabilities, which allows dAMP incorporation to proceed in a manner similar to that observed opposite abasic sites. The Miscoding Potential of 5-Hydroxycytosine Arises Due to Template Instability in the Replicative Polymerase Active Site.,Zahn KE, Averill A, Wallace SS, Doublie S Biochemistry. 2011 Nov 3. PMID:22026756[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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