7n8s: Difference between revisions
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New page: '''Unreleased structure''' The entry 7n8s is ON HOLD Authors: Korolev, S., Miller, I. Description: LINE-1 endonuclease domain complex with DNA Category: Unreleased Structures [[Cat... |
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==LINE-1 endonuclease domain complex with DNA== | |||
<StructureSection load='7n8s' size='340' side='right'caption='[[7n8s]], [[Resolution|resolution]] 2.79Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[7n8s]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7N8S OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7N8S 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]] 2.79Å</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=7n8s FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7n8s OCA], [https://pdbe.org/7n8s PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7n8s RCSB], [https://www.ebi.ac.uk/pdbsum/7n8s PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7n8s ProSAT]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Long interspersed nuclear element-1 (L1) is an autonomous non-LTR retrotransposon comprising approximately 20% of the human genome. L1 self-propagation causes genomic instability and is strongly associated with aging, cancer and other diseases. The endonuclease domain of L1's ORFp2 protein (L1-EN) initiates de novo L1 integration by nicking the consensus sequence 5'-TTTTT/AA-3'. In contrast, related nucleases including structurally conserved apurinic/apyrimidinic endonuclease 1 (APE1) are non-sequence specific. To investigate mechanisms underlying sequence recognition and catalysis by L1-EN, we solved crystal structures of L1-EN complexed with DNA substrates. This showed that conformational properties of the preferred sequence drive L1-EN's sequence-specificity and catalysis. Unlike APE1, L1-EN does not bend the DNA helix, but rather causes 'compression' near the cleavage site. This provides multiple advantages for L1-EN's role in retrotransposition including facilitating use of the nicked poly-T DNA strand as a primer for reverse transcription. We also observed two alternative conformations of the scissile bond phosphate, which allowed us to model distinct conformations for a nucleophilic attack and a transition state that are likely applicable to the entire family of nucleases. This work adds to our mechanistic understanding of L1-EN and related nucleases and should facilitate development of L1-EN inhibitors as potential anticancer and antiaging therapeutics. | |||
Structural dissection of sequence recognition and catalytic mechanism of human LINE-1 endonuclease.,Miller I, Totrov M, Korotchkina L, Kazyulkin DN, Gudkov AV, Korolev S Nucleic Acids Res. 2021 Sep 23. pii: 6374484. doi: 10.1093/nar/gkab826. PMID:34554261<ref>PMID:34554261</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: Korolev | <div class="pdbe-citations 7n8s" style="background-color:#fffaf0;"></div> | ||
[[Category: Miller | == References == | ||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: Korolev S]] | |||
[[Category: Miller I]] | |||
Latest revision as of 08:59, 17 October 2024
LINE-1 endonuclease domain complex with DNA
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