ArticleProceedings of the National Academy of Sciences of the United States of America2003
Crystal structures that suggest late development of genetic code components for differentiating aromatic side chains.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
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50 citing papers in PubMed.
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- Thermal Titration Molecular Dynamics: The Revenge of the Fragments.Journal of chemical information and modeling · 2025Article
- An asymmetric structure of bacterial TrpRS supports the half-of-the-sites catalytic mechanism and facilitates antimicrobial screening.Nucleic acids research · 2023Article
- Mechanistic perspectives on anti-aminoacyl-tRNA synthetase syndrome.Trends in biochemical sciences · 2023Review
- Peculiarities of aminoacyl-tRNA synthetases from trypanosomatids.The Journal of biological chemistry · 2021Article
- Enzyme catalysis prior to aromatic residues: Reverse engineering of a dephospho-CoA kinase.Protein science : a publication of the Protein Society · 2021Article
- The structural basis of the genetic code: amino acid recognition by aminoacyl-tRNA synthetases.Scientific reports · 2020Article
- Aminoacyl tRNA synthetases as potential drug targets of the Panthera pathogen Babesia.Parasites & vectors · 2019Article
- Neurodegenerative Charcot-Marie-Tooth disease as a case study to decipher novel functions of aminoacyl-tRNA synthetases.The Journal of biological chemistry · 2019Review
- Homozygosity for a mutation affecting the catalytic domain of tyrosyl-tRNA synthetase (YARS) causes multisystem disease.Human molecular genetics · 2019Article
- Aminoacyl tRNA synthetases as malarial drug targets: a comparative bioinformatics study.Malaria journal · 2019Article
- Tryptophanyl-tRNA synthetase mediates high-affinity tryptophan uptake into human cells.The Journal of biological chemistry · 2018Article
- Modern diversification of the amino acid repertoire driven by oxygen.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Bioinformatic Analysis Reveals Archaeal tRNALife (Basel, Switzerland) · 2017Article
- Identification of a residue crucial for the angiostatic activity of human mini tryptophanyl-tRNA synthetase by focusing on its molecular evolution.Scientific reports · 2016Article
- Selective Inhibition of Bacterial Tryptophanyl-tRNA Synthetases by Indolmycin Is Mechanism-based.The Journal of biological chemistry · 2016Article
- The place of RNA in the origin and early evolution of the genetic machinery.Life (Basel, Switzerland) · 2014Article
- Expression, purification, and characterization of rhTyrRS.BMC biotechnology · 2014Article
- Structural disorder in expanding the functionome of aminoacyl-tRNA synthetases.Chemistry & biology · 2013Review
- Small-angle X-ray solution scattering study of the multi-aminoacyl-tRNA synthetase complex reveals an elongated and multi-armed particle.The Journal of biological chemistry · 2013Article
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6 authors.
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Abstract
Early forms of the genetic code likely generated "statistical" proteins, with similar side chains occupying the same sequence positions at different ratios. In this scenario, groups of related side chains were treated by aminoacyl-tRNA synthetases as a single molecular species until a discrimination mechanism developed that could separate them. The aromatic amino acids tryptophan, tyrosine, and phenylalanine likely constituted one of these groups. A crystal structure of human tryptophanyl-tRNA synthetase was solved at 2.1 A with a tryptophanyl-adenylate bound at the active site. A cocrystal structure of an active fragment of human tyrosyl-tRNA synthetase with its cognate amino acid analog was also solved at 1.6 A. The two structures enabled active site identifications and provided the information for structure-based sequence alignments of approximately 45 orthologs of each enzyme. Two critical positions shared by all tyrosyl-tRNA synthetases and tryptophanyl-tRNA synthetases for amino acid discrimination were identified. The variations at these two positions and phylogenetic analyses based on the structural information suggest that, in contrast to many other amino acids, discrimination of tyrosine from tryptophan occurred late in the development of the genetic code.
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