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Genomic database furnishes a spontaneous example of a functional Class II glycyl-tRNA synthetase urzyme.
Patra, Sourav Kumar; Douglas, Jordan; Wills, Peter R; Bouckeart, Remco; Betts, Laurie; Qing, Tang Guo; Carter, Charles W.
Afiliação
  • Patra SK; Department of Biochemistry and Biophysics, University of North Carolina, Chapel Hill, NC 27599-7260.
  • Douglas J; Department of Physics, The University of Auckland, New Zealand.
  • Wills PR; Centre for Computational Evolution, University of Auckland, New Zealand.
  • Bouckeart R; Department of Physics, The University of Auckland, New Zealand.
  • Betts L; Centre for Computational Evolution, University of Auckland, New Zealand.
  • Qing TG; Department of Computer Science, The University of Auckland, New Zealand.
  • Carter CW; Department of Biochemistry and Biophysics, University of North Carolina, Chapel Hill, NC 27599-7260.
bioRxiv ; 2024 Jan 13.
Article em En | MEDLINE | ID: mdl-38260702
ABSTRACT
The chief barrier to studies of how genetic coding emerged is the lack of experimental models for ancestral aminoacyl-tRNA synthetases (AARS). We hypothesized that conserved core catalytic sites could represent such ancestors. That hypothesis enabled engineering functional "urzymes" from TrpRS, LeuRS, and HisRS. We describe here a fourth urzyme, GlyCA, detected in an open reading frame from the genomic record of the arctic fox, Vulpes lagopus. GlyCA is homologous to a bacterial heterotetrameric Class II GlyRS-B. Alphafold2 predicted that the N-terminal 81 amino acids would adopt a 3D structure nearly identical to the HisRS urzyme (HisCA1). We expressed and purified that N-terminal segment. Enzymatic characterization revealed a robust single-turnover burst size and a catalytic rate for ATP consumption well in excess of that previously published for HisCA1. Time-dependent aminoacylation of tRNAGly proceeds at a rate consistent with that observed for amino acid activation. In fact, GlyCA is actually 35 times more active in glycine activation by ATP than the full-length GlyRS-B α-subunit dimer. ATP-dependent activation of the 20 canonical amino acids favors Class II amino acids that complement those favored by HisCA and LeuAC. These properties reinforce the notion that urzymes represent the requisite ancestral catalytic activities to implement a reduced genetic coding alphabet.
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Texto completo: 1 Base de dados: MEDLINE Tipo de estudo: Prognostic_studies Idioma: En Revista: BioRxiv Ano de publicação: 2024 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Tipo de estudo: Prognostic_studies Idioma: En Revista: BioRxiv Ano de publicação: 2024 Tipo de documento: Article