8sp5: Difference between revisions
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==LINE-1 retrotransposon endonuclease domain complex with Mn2+== | |||
<StructureSection load='8sp5' size='340' side='right'caption='[[8sp5]], [[Resolution|resolution]] 2.23Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[8sp5]] is a 2 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=8SP5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8SP5 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]] 2.23Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=8sp5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8sp5 OCA], [https://pdbe.org/8sp5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8sp5 RCSB], [https://www.ebi.ac.uk/pdbsum/8sp5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8sp5 ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/V9H0D0_HUMAN V9H0D0_HUMAN] | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The long interspersed nuclear element-1 (LINE-1 or L1) retrotransposon is the only active autonomously replicating retrotransposon in the human genome. L1 harms the cell by inserting new copies, generating DNA damage, and triggering inflammation. Therefore, L1 inhibition could be used to treat many diseases associated with these processes. Previous research has focused on inhibition of the L1 reverse transcriptase due to the prevalence of well-characterized inhibitors of related viral enzymes. Here we present the L1 endonuclease as another target for reducing L1 activity. We characterize structurally diverse small molecule endonuclease inhibitors using computational, biochemical, and biophysical methods. We also show that these inhibitors reduce L1 retrotransposition, L1-induced DNA damage, and inflammation reinforced by L1 in senescent cells. These inhibitors could be used for further pharmacological development and as tools to better understand the life cycle of this element and its impact on disease processes. | |||
Identification and characterization of small molecule inhibitors of the LINE-1 retrotransposon endonuclease.,D'Ordine AM, Jogl G, Sedivy JM Nat Commun. 2024 May 8;15(1):3883. doi: 10.1038/s41467-024-48066-x. PMID:38719805<ref>PMID:38719805</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: D | <div class="pdbe-citations 8sp5" style="background-color:#fffaf0;"></div> | ||
[[Category: | == References == | ||
[[Category: | <references/> | ||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: D'Ordine AM]] | |||
[[Category: Jogl G]] | |||
[[Category: Sedivy JM]] | |||
Latest revision as of 11:05, 22 May 2024
LINE-1 retrotransposon endonuclease domain complex with Mn2+LINE-1 retrotransposon endonuclease domain complex with Mn2+
Structural highlights
FunctionPublication Abstract from PubMedThe long interspersed nuclear element-1 (LINE-1 or L1) retrotransposon is the only active autonomously replicating retrotransposon in the human genome. L1 harms the cell by inserting new copies, generating DNA damage, and triggering inflammation. Therefore, L1 inhibition could be used to treat many diseases associated with these processes. Previous research has focused on inhibition of the L1 reverse transcriptase due to the prevalence of well-characterized inhibitors of related viral enzymes. Here we present the L1 endonuclease as another target for reducing L1 activity. We characterize structurally diverse small molecule endonuclease inhibitors using computational, biochemical, and biophysical methods. We also show that these inhibitors reduce L1 retrotransposition, L1-induced DNA damage, and inflammation reinforced by L1 in senescent cells. These inhibitors could be used for further pharmacological development and as tools to better understand the life cycle of this element and its impact on disease processes. Identification and characterization of small molecule inhibitors of the LINE-1 retrotransposon endonuclease.,D'Ordine AM, Jogl G, Sedivy JM Nat Commun. 2024 May 8;15(1):3883. doi: 10.1038/s41467-024-48066-x. PMID:38719805[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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