ArticleThe Journal of biological chemistry2010
Tryptophanyl-tRNA synthetase Urzyme: a model to recapitulate molecular evolution and investigate intramolecular complementation.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed.
- Reduced Amino Acid Substitution Matrices Find Traces of Ancient Coding Alphabets in Modern Day Proteins.Molecular biology and evolution · 2025Article
- Aminoacyl-tRNA synthetase urzymes optimized by deep learning behave as a quasispecies.Structural dynamics (Melville, N.Y.) · 2025Article
- A genomic database furnishes minimal functional glycyl-tRNA synthetases homologous to other, designed class II urzymes.Nucleic acids research · 2024Article
- Primordial aminoacyl-tRNA synthetases preferred minihelices to full-length tRNA.Nucleic acids research · 2024Article
- Base Pairing Promoted the Self-Organization of Genetic Coding, Catalysis, and Free-Energy Transduction.Life (Basel, Switzerland) · 2024Review
- Genomic database furnishes a spontaneous example of a functional Class II glycyl-tRNA synthetase urzyme.bioRxiv : the preprint server for biology · 2024Article
- Domain acquisition by class I aminoacyl-tRNA synthetase urzymes coordinated the catalytic functions of HVGH and KMSKS motifs.Nucleic acids research · 2023Article
- Microcalorimetry reveals multi-state thermal denaturation ofStructural dynamics (Melville, N.Y.) · 2023Article
- On the Origins of Enzymes: Phosphate-Binding Polypeptides Mediate Phosphoryl Transfer to Synthesize Adenosine Triphosphate.Journal of the American Chemical Society · 2023Article
- A Leucyl-tRNA Synthetase Urzyme: Authenticity of tRNA Synthetase Catalytic Activities and Promiscuous Phosphorylation of Leucyl-5'AMP.International journal of molecular sciences · 2022Article
- Amino Acid Specificity of Ancestral Aminoacyl-tRNA Synthetase Prior to the Last Universal Common Ancestor Commonote commonote.Journal of molecular evolution · 2022Article
- Multidimensional Phylogenetic Metrics Identify Class I Aminoacyl-tRNA Synthetase Evolutionary Mosaicity and Inter-Modular Coupling.International journal of molecular sciences · 2022Article
- Helicase-like functions in phosphate loop containing beta-alpha polypeptides.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Reciprocally-Coupled Gating: Strange Loops in Bioenergetics, Genetics, and Catalysis.Biomolecules · 2021Review
- Aminoacyl-tRNA synthetases.RNA (New York, N.Y.) · 2020Review
- Experimental solutions to problems defining the origin of codon-directed protein synthesis.Bio Systems · 2019Review
- Review
- A Proposal of the Ur-proteome.Origins of life and evolution of the biosphere : the journal of the International Society for the Study of the Origin of Life · 2018Article
- Interdependence, Reflexivity, Fidelity, Impedance Matching, and the Evolution of Genetic Coding.Molecular biology and evolution · 2018Article
- High-Dimensional Mutant and Modular Thermodynamic Cycles, Molecular Switching, and Free Energy Transduction.Annual review of biophysics · 2017Review
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6 authors.
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Abstract
We substantiate our preliminary description of the class I tryptophanyl-tRNA synthetase minimal catalytic domain with details of its construction, structure, and steady-state kinetic parameters. Generating that active fragment involved deleting 65% of the contemporary enzyme, including the anticodon-binding domain and connecting peptide 1, CP1, a 74-residue internal segment from within the Rossmann fold. We used protein design (Rosetta), rather than phylogenetic sequence alignments, to identify mutations to compensate for the severe loss of modularity, thus restoring stability, as evidenced by renaturation described previously and by 70-ns molecular dynamics simulations. Sufficient solubility to enable biochemical studies was achieved by expressing the redesigned Urzyme as a maltose-binding protein fusion. Michaelis-Menten kinetic parameters from amino acid activation assays showed that, compared with the native full-length enzyme, TrpRS Urzyme binds ATP with similar affinity. This suggests that neither of the two deleted structural modules has a strong influence on ground-state ATP binding. However, tryptophan has 10(3) lower affinity, and the Urzyme has comparably reduced specificity relative to the related amino acid, tyrosine. Molecular dynamics simulations revealed how CP1 may contribute significantly to cognate amino acid specificity. As class Ia editing domains are nested within the CP1, this finding suggests that this module enhanced amino acid specificity continuously, throughout their evolution. We call this type of reconstructed protein catalyst an Urzyme (Ur prefix indicates original, primitive, or earliest). It establishes a model for recapitulating very early steps in molecular evolution in which fitness may have been enhanced by accumulating entire modules, rather than by discrete amino acid sequence changes.
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