ArticleRNA (New York, N.Y.)2006
Structure-guided mutational analysis of T4 RNA ligase 1.
Article in RNA (New York, N.Y.), 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 27 citations in OpenAlex.
- PAR-dCLIP: Enabling detection of RNA binding protein target transcripts bound at 5' termini through the incorporation of a decapping step.Methods in enzymology · 2024Article
- A scenario for the emergence of protoviroids in the RNA world and for their further evolution into viroids and viroid-like RNAs by modular recombinations and mutations.Virus evolution · 2022Review
- Caveat mutator: alanine substitutions for conserved amino acids in RNA ligase elicit unexpected rearrangements of the active site for lysine adenylylation.Nucleic acids research · 2020Article
- Structures of DNA-bound human ligase IV catalytic core reveal insights into substrate binding and catalysis.Nature communications · 2018Article
- Two-metal versus one-metal mechanisms of lysine adenylylation by ATP-dependent and NADProceedings of the National Academy of Sciences of the United States of America · 2017Article
- Things Are Getting Hairy: Enterobacteria Bacteriophage vB_PcaM_CBB.Frontiers in microbiology · 2017Article
- Structural and mutational analysis of archaeal ATP-dependent RNA ligase identifies amino acids required for RNA binding and catalysis.Nucleic acids research · 2016Article
- Viroid RNA redirects host DNA ligase 1 to act as an RNA ligase.Proceedings of the National Academy of Sciences of the United States of America · 2012Article
- Kinetic analysis of 3'-5' nucleotide addition catalyzed by eukaryotic tRNA(His) guanylyltransferase.Biochemistry · 2012Article
- Archaeal 3'-phosphate RNA splicing ligase characterization identifies the missing component in tRNA maturation.Proceedings of the National Academy of Sciences of the United States of America · 2011Article
- Article
- Structure-guided Mutational Analysis of the Nucleotidyltransferase Domain of Escherichia coli DNA Ligase (LigA).The Journal of biological chemistry · 2009Article
- Monomeric linear RNA of citrus exocortis viroid resulting from processing in vivo has 5'-phosphomonoester and 3'-hydroxyl termini: implications for the RNase and RNA ligase involved in replication.Journal of virology · 2008Article
- RNA repair: an antidote to cytotoxic eukaryal RNA damage.Molecular cell · 2008Article
- The C-terminal domain of T4 RNA ligase 1 confers specificity for tRNA repair.RNA (New York, N.Y.) · 2007Article
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
T4 RNA ligase 1 (Rnl1) is a tRNA repair enzyme that circumvents an RNA-damaging host antiviral response. Whereas the three-step reaction scheme of Rnl1 is well established, the structural basis for catalysis has only recently been appreciated as mutational and crystallographic approaches have converged. Here we performed a structure-guided alanine scan of nine conserved residues, including side chains that either contact the ATP substrate via adenine (Leu179, Val230), the 2'-OH (Glu159), or the gamma phosphate (Tyr37) or coordinate divalent metal ions at the ATP alpha phosphate (Glu159, Tyr246) or beta phosphate (Asp272, Asp273). We thereby identified Glu159 and Tyr246 as essential for RNA sealing activity in vitro and for tRNA repair in vivo. Structure-activity relationships at Glu159 and Tyr246 were clarified by conservative substitutions. Eliminating the phosphate-binding Tyr37, and the magnesium-binding Asp272 and Asp273 side chains had little impact on sealing activity in vitro or in vivo, signifying that not all atomic interactions in the active site are critical for function. Analysis of mutational effects on individual steps of the ligation pathway underscored how different functional groups come into play during the ligase-adenylylation reaction versus the subsequent steps of RNA-adenylylation and phosphodiester formation. Moreover, the requirements for sealing exogenous preformed RNA-adenylate are more stringent than are those for sealing the RNA-adenylate intermediate formed in situ during ligation of a 5'-PO4 RNA.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.