8vzm

DNA Ligase 1 captured with pre-step 3 ligation at the rA:T nicksite

spinqualitylabelsall models 8vzm, resolution 2.51Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 8vzm is a 4 chain structure with sequence from Homo sapiens and Synthetic construct. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.51Å Ligands: AMP Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function DNLI1_HUMAN DNA ligase that seals nicks in double-stranded DNA during DNA replication, DNA recombination and DNA repair. Publication Abstract from PubMed Human DNA ligase 1 (LIG1) is the main replicative ligase that seals Okazaki fragments during nuclear replication and finalizes DNA repair pathways by joining DNA ends of the broken strand breaks in the three steps of the ligation reaction. LIG1 can tolerate the RNA strand upstream of the nick, yet an atomic insight into the sugar discrimination mechanism by LIG1 against a ribonucleotide at the 3'-terminus of nick DNA is unknown. Here, we determined X-ray structures of LIG1/3'-RNA-DNA hybrids and captured the ligase during pre- and post-step 3 the ligation reaction. Furthermore, the overlays of 3'-rA:T and 3'-rG:C step 3 structures with step 2 structures of canonical 3'-dA:T and 3'-dG:C uncover a network of LIG1/DNA interactions through Asp570 and Arg871 side chains with 2'-OH of the ribose at nick showing a final phosphodiester bond formation and the other ligase active site residues surrounding the AMP site. Finally, we demonstrated that LIG1 can ligate the nick DNA substrates with pre-inserted 3'-ribonucleotides as efficiently as Watson-Crick base-paired ends in vitro. Together, our findings uncover a novel atomic insight into a lack of sugar discrimination by LIG1 and the impact of improper sugar on the nick sealing of ribonucleotides at the last step of DNA replication and repair. Structures of LIG1 provide a mechanistic basis for understanding a lack of sugar discrimination against a ribonucleotide at the 3'-end of nick DNA.,Balu KE, Gulkis M, Almohdar D, Caglayan M J Biol Chem. 2024 Mar 24;300(5):107216. doi: 10.1016/j.jbc.2024.107216. PMID:38522520 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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