6p09: Difference between revisions
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==Human DNA Ligase 1 Bound to an Adenylated, dideoxy Terminated DNA nick with 200 mM Mg2+== | |||
<StructureSection load='6p09' size='340' side='right'caption='[[6p09]], [[Resolution|resolution]] 2.05Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[6p09]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] 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=6P09 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6P09 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]] 2.052Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=AMP:ADENOSINE+MONOPHOSPHATE'>AMP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</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=6p09 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6p09 OCA], [https://pdbe.org/6p09 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6p09 RCSB], [https://www.ebi.ac.uk/pdbsum/6p09 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6p09 ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/DNLI1_HUMAN DNLI1_HUMAN] DNA ligase that seals nicks in double-stranded DNA during DNA replication, DNA recombination and DNA repair. | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
DNA ligases catalyze the joining of DNA strands to complete DNA replication, recombination and repair transactions. To protect the integrity of the genome, DNA ligase 1 (LIG1) discriminates against DNA junctions harboring mutagenic 3'-DNA mismatches or oxidative DNA damage, but how such high-fidelity ligation is enforced is unknown. Here, X-ray structures and kinetic analyses of LIG1 complexes with undamaged and oxidatively damaged DNA unveil that LIG1 employs Mg(2+)-reinforced DNA binding to validate DNA base pairing during the adenylyl transfer and nick-sealing ligation reaction steps. Our results support a model whereby LIG1 fidelity is governed by a high-fidelity (HiFi) interface between LIG1, Mg(2+), and the DNA substrate that tunes the enzyme to release pro-mutagenic DNA nicks. In a second tier of protection, LIG1 activity is surveilled by Aprataxin (APTX), which suppresses mutagenic and abortive ligation at sites of oxidative DNA damage. | |||
Two-tiered enforcement of high-fidelity DNA ligation.,Tumbale PP, Jurkiw TJ, Schellenberg MJ, Riccio AA, O'Brien PJ, Williams RS Nat Commun. 2019 Nov 28;10(1):5431. doi: 10.1038/s41467-019-13478-7. PMID:31780661<ref>PMID:31780661</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 6p09" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[DNA ligase 3D structures|DNA ligase 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: Synthetic construct]] | |||
[[Category: Riccio AA]] | |||
[[Category: Schellenberg MJ]] | |||
[[Category: Tumbale PS]] | |||
[[Category: Williams RS]] | |||
Latest revision as of 10:20, 11 October 2023
Human DNA Ligase 1 Bound to an Adenylated, dideoxy Terminated DNA nick with 200 mM Mg2+Human DNA Ligase 1 Bound to an Adenylated, dideoxy Terminated DNA nick with 200 mM Mg2+
Structural highlights
FunctionDNLI1_HUMAN DNA ligase that seals nicks in double-stranded DNA during DNA replication, DNA recombination and DNA repair. Publication Abstract from PubMedDNA ligases catalyze the joining of DNA strands to complete DNA replication, recombination and repair transactions. To protect the integrity of the genome, DNA ligase 1 (LIG1) discriminates against DNA junctions harboring mutagenic 3'-DNA mismatches or oxidative DNA damage, but how such high-fidelity ligation is enforced is unknown. Here, X-ray structures and kinetic analyses of LIG1 complexes with undamaged and oxidatively damaged DNA unveil that LIG1 employs Mg(2+)-reinforced DNA binding to validate DNA base pairing during the adenylyl transfer and nick-sealing ligation reaction steps. Our results support a model whereby LIG1 fidelity is governed by a high-fidelity (HiFi) interface between LIG1, Mg(2+), and the DNA substrate that tunes the enzyme to release pro-mutagenic DNA nicks. In a second tier of protection, LIG1 activity is surveilled by Aprataxin (APTX), which suppresses mutagenic and abortive ligation at sites of oxidative DNA damage. Two-tiered enforcement of high-fidelity DNA ligation.,Tumbale PP, Jurkiw TJ, Schellenberg MJ, Riccio AA, O'Brien PJ, Williams RS Nat Commun. 2019 Nov 28;10(1):5431. doi: 10.1038/s41467-019-13478-7. PMID:31780661[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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