ArticleThe Journal of biological chemistry2009
Crystal structures and biochemical analyses suggest a unique mechanism and role for human glycyl-tRNA synthetase in Ap4A homeostasis.
Article in The Journal of biological chemistry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 42 citations in OpenAlex.
- Binding of Glycyl-tRNA synthetase to Mengovirus RNA stimulates translation.Nucleic acids research · 2026Article
- Integrating traditional QSAR and read-across-based regression models for predicting potential anti-leishmanial azole compounds.Molecular diversity · 2025Article
- Investigation of the Structure and Functional Activity of the YqeK Protein inMicroorganisms · 2025Article
- Article
- Structural basis of a two-step tRNA recognition mechanism for plastid glycyl-tRNA synthetase.Nucleic acids research · 2023Article
- Fraisinib: a calixpyrrole derivative reducing A549 cell-derived NSCLC tumorFrontiers in pharmacology · 2023Article
- Elusive Trans-Acting Factors Which Operate with Type I (Poliovirus-like) IRES Elements.International journal of molecular sciences · 2022Review
- Re-evaluation of Diadenosine Tetraphosphate (ApFrontiers in molecular biosciences · 2020Review
- Peripheral neuropathy via mutant tRNA synthetases: Inhibition of protein translation provides a possible explanation.BioEssays : news and reviews in molecular, cellular and developmental biology · 2016Review
- Neddylation requires glycyl-tRNA synthetase to protect activated E2.Nature structural & molecular biology · 2016Article
- Large Conformational Changes of Insertion 3 in Human Glycyl-tRNA Synthetase (hGlyRS) during Catalysis.The Journal of biological chemistry · 2016Article
- Evolutionary Limitation and Opportunities for Developing tRNA Synthetase Inhibitors with 5-Binding-Mode Classification.Life (Basel, Switzerland) · 2015Review
- Cocrystal structures of glycyl-tRNA synthetase in complex with tRNA suggest multiple conformational states in glycylation.The Journal of biological chemistry · 2014Article
- Structural disorder in expanding the functionome of aminoacyl-tRNA synthetases.Chemistry & biology · 2013Review
- The crystal structures of the α-subunit of the α(2)β (2) tetrameric Glycyl-tRNA synthetase.Journal of structural and functional genomics · 2012Article
- Proteomic analysis of the nuclear phosphorylated proteins in dairy cow mammary epithelial cells treated with estrogen.In vitro cellular & developmental biology. Animal · 2012Article
- Glycyl-tRNA synthetase specifically binds to the poliovirus IRES to activate translation initiation.Nucleic acids research · 2012Article
- Side chain independent recognition of aminoacyl adenylates by the Hint1 transcription suppressor.The journal of physical chemistry. B · 2012Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Aminoacyl-tRNA synthetases catalyze the attachment of amino acids to their cognate tRNAs for protein synthesis. However, the aminoacylation reaction can be diverted to produce diadenosine tetraphosphate (Ap4A), a universal pleiotropic signaling molecule needed for cell regulation pathways. The only known mechanism for Ap4A production by a tRNA synthetase is through the aminoacylation reaction intermediate aminoacyl-AMP, thus making Ap4A synthesis amino acid-dependent. Here, we demonstrate a new mechanism for Ap4A synthesis. Crystal structures and biochemical analyses show that human glycyl-tRNA synthetase (GlyRS) produces Ap4A by direct condensation of two ATPs, independent of glycine concentration. Interestingly, whereas the first ATP-binding pocket is conserved for all class II tRNA synthetases, the second ATP pocket is formed by an insertion domain that is unique to GlyRS, suggesting that GlyRS is the only tRNA synthetase catalyzing direct Ap4A synthesis. A special role for GlyRS in Ap4A homeostasis is proposed.
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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.