ArticleRNA (New York, N.Y.)2016
Characterization of the tRNA ligases of pathogenic fungi Aspergillus fumigatus and Coccidioides immitis.
Article in RNA (New York, N.Y.), 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 15 citations in OpenAlex.
- 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
- 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
- A Comprehensive Insight into Fungal Enzymes: Structure, Classification, and Their Role in Mankind's Challenges.Journal of fungi (Basel, Switzerland) · 2021Review
- 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
- Structure and two-metal mechanism of fungal tRNA ligase.Nucleic acids research · 2019Article
- Characterization of the molecular crosstalk within the essential Grc3/Las1 pre-rRNA processing complex.RNA (New York, N.Y.) · 2018Article
- Structural basis for the GTP specificity of the RNA kinase domain of fungal tRNA ligase.Nucleic acids research · 2017Article
- Characterization of Runella slithyformis HD-Pnk, a Bifunctional DNA/RNA End-Healing Enzyme Composed of an N-Terminal 2',3'-Phosphoesterase HD Domain and a C-Terminal 5'-OH Polynucleotide Kinase Domain.Journal of bacteriology · 2017Article
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
Yeast tRNA ligase (Trl1) is an essential trifunctional enzyme that repairs RNA breaks with 2',3'-cyclic-PO4 and 5'-OH ends. Trl1 is composed of C-terminal cyclic phosphodiesterase and central polynucleotide kinase domains that heal the broken ends to generate the 3'-OH, 2'-PO4, and 5'-PO4 termini required for sealing by an N-terminal ligase domain. Trl1 enzymes are found in all human fungal pathogens and they are promising targets for antifungal drug discovery because: (i) their domain structures and biochemical mechanisms are unique compared to the mammalian RtcB-type tRNA splicing enzyme; and (ii) there are no obvious homologs of the Trl1 ligase domain in mammalian proteomes. Here we characterize the tRNA ligases of two human fungal pathogens: Coccidioides immitis and Aspergillus fumigatus The biological activity of CimTrl1 and AfuTrl1 was verified by showing that their expression complements a Saccharomyces cerevisiae trl1Δ mutant. Purified recombinant AfuTrl1 and CimTrl1 proteins were catalytically active in joining 2',3'-cyclic-PO4 and 5'-OH ends in vitro, either as full-length proteins or as a mixture of separately produced healing and sealing domains. The biochemical properties of CimTrl1 and AfuTrl1 are similar to those of budding yeast Trl1, particularly with respect to their preferential use of GTP as the phosphate donor for the polynucleotide kinase reaction. Our findings provide genetic and biochemical tools to screen for inhibitors of tRNA ligases from pathogenic fungi.
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