ArticleNucleic acids research2019
Structure and two-metal mechanism of fungal tRNA ligase.
Article in Nucleic acids research, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 15 citations in OpenAlex.
- Structural framework for the assembly of the human tRNA ligase complex.Nature communications · 2026Article
- Enzymology of the metazoan tRNA ligase complex: a lifetime in cycles.Cellular and molecular life sciences : CMLS · 2026Review
- Advances in molecular tools for elucidating nucleic acid biology in fungal pathogens.microLife · 2026Review
- Interdomain assembly between the fungal tRNA ligase adenylyltransferase and kinase domain.RNA (New York, N.Y.) · 2025Article
- Structure of fungal tRNA ligase Trl1 with RNA reveals conserved substrate-binding principles.Nature structural & molecular biology · 2025Article
- The adaptability of the fungal tRNA ligase's ATP-binding pocket: a potential target for new antifungal drugs.NAR molecular medicine · 2025Article
- Discovery of novel targets for important human and plant fungal pathogens via an automated computational pipeline HitList.PloS one · 2025Article
- Identification, characterization, and structure of a tRNA splicing enzyme RNA 5'-OH kinase from the pathogenic fungi Mucorales.RNA (New York, N.Y.) · 2024Article
- Kinetic and structural insights into the requirement of fungal tRNA ligase for a 2'-phosphate end.RNA (New York, N.Y.) · 2024Article
- Characterisation and engineering of a thermophilic RNA ligase from Palaeococcus pacificus.Nucleic acids research · 2024Article
- Fungi of the order Mucorales express a "sealing-only" tRNA ligase.RNA (New York, N.Y.) · 2024Article
- Characterization of tRNA splicing enzymes RNA ligase and tRNA 2'-phosphotransferase from the pathogenic fungi Mucorales.RNA (New York, N.Y.) · 2024Article
- Fungi of the order Mucorales express a "sealing-only" tRNA ligase.bioRxiv : the preprint server for biology · 2023Article
- The life and times of a tRNA.RNA (New York, N.Y.) · 2023Review
- Crystal Structures of Flavivirus NS5 Guanylyltransferase Reveal a GMP-Arginine Adduct.Journal of virology · 2022Article
- A Comprehensive Insight into Fungal Enzymes: Structure, Classification, and Their Role in Mankind's Challenges.Journal of fungi (Basel, Switzerland) · 2021Review
- Article
- 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
- Atomic structures of the RNA end-healing 5'-OH kinase and 2',3'-cyclic phosphodiesterase domains of fungal tRNA ligase: conformational switches in the kinase upon binding of the GTP phosphate donor.Nucleic acids research · 2019Article
- Structures of ATP-bound DNA ligase D in a closed domain conformation reveal a network of amino acid and metal contacts to the ATP phosphates.The Journal of biological chemistry · 2019Article
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Authors and funding
4 authors at 1 institution in 1 country.
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Abstract
Fungal tRNA ligase (Trl1) is an essential enzyme that repairs RNA breaks with 2',3'-cyclic-PO4 and 5'-OH ends inflicted during tRNA splicing and non-canonical mRNA splicing in the fungal unfolded protein response. Trl1 is composed of C-terminal cyclic phosphodiesterase (CPD) and central GTP-dependent polynucleotide kinase (KIN) domains that heal the broken ends to generate the 3'-OH,2'-PO4 and 5'-PO4 termini required for sealing by an N-terminal ATP-dependent ligase domain (LIG). Here we report crystal structures of the Trl1-LIG domain from Chaetomium thermophilum at two discrete steps along the reaction pathway: the covalent LIG-(lysyl-Nζ)-AMP•Mn2+ intermediate and a LIG•ATP•(Mn2+)2 Michaelis complex. The structures highlight a two-metal mechanism whereby a penta-hydrated metal complex stabilizes the transition state of the ATP α phosphate and a second metal bridges the β and γ phosphates to help orient the pyrophosphate leaving group. A LIG-bound sulfate anion is a plausible mimetic of the essential RNA terminal 2'-PO4. Trl1-LIG has a distinctive C-terminal domain that instates fungal Trl1 as the founder of an Rnl6 clade of ATP-dependent RNA ligase. We discuss how the Trl1-LIG structure rationalizes the large body of in vivo structure-function data for Saccharomyces cerevisiae Trl1.
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