8sp5

LINE-1 retrotransposon endonuclease domain complex with Mn2+

spinqualitylabelsall models 8sp5, resolution 2.23Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 8sp5 is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.23Å Ligands: MN, SO4 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function V9H0D0_HUMAN 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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