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  • inhibitors
  • Thus, HF is a new type of ATP-dependent inhibitor that simultaneously occupies two different substrate binding sites on ProRS.Moreover, our structure indicates a possible similar mechanism of action for febrifugine in malaria treatment.Finally, the elucidation here of a two-site modular targeting activity of HF raises the possibility that substrate-directed capture of similar inhibitors might be a general mechanism that could be applied to other synthetases. (nih.gov)
  • Finally, the elucidation here of a two-site modular targeting activity of HF raises the possibility that substrate-directed capture of similar inhibitors might be a general mechanism that could be applied to other synthetases. (nih.gov)
  • sequence
  • The class I synthetases are further divided into three subclasses, a, b and c, according to sequence homology. (semanticscholar.org)
  • The remaining divergence in the amino acid sequence of KDO8PSs is apparently unrelated to the underlying catalytic mechanism. (jove.com)
  • Although the functionality of a given protein is the direct consequence of its unique amino acid sequence, it is only realized by the folding of the polypeptide chain into a single defined three-dimensional arrangement or more commonly into an ensemble of interconverting conformations. (jove.com)
  • adenosine
  • It aminoacylates at the 2'-OH of a terminal adenosine nucleotide on tRNA, and it is usually monomeric or dimeric (one or two subunits, respectively). (wikipedia.org)
  • It aminoacylates at the 3'-OH of a terminal adenosine on tRNA, and is usually dimeric or tetrameric (two or four subunits, respectively). (wikipedia.org)
  • McC is a heptapeptide with a formylated N-terminal methionine and a C-terminal aspartate whose α-carboxyl group is covalently linked to adenosine through an N -acyl phosphoramide bond ( 10 , 14 ). (asm.org)
  • mutation
  • The identified mutation spectrum suggests that only mutation types that allow some residual tRNA-charging activity can result in the described mtARS diseases but the molecular mechanisms behind the selective tissue involvement are not currently understood. (nih.gov)
  • anticodon
  • In a typical scenario, an aaRS consists of a catalytic domain (where both the above reactions take place) and an anticodon binding domain (which interacts mostly with the anticodon region of the tRNA and ensures binding of the correct tRNA to the amino acid). (wikipedia.org)
  • pathway
  • Recently, HF was reported to inhibit T(H)17 cell differentiation by activating the amino acid response pathway, through inhibiting human prolyl-transfer RNA synthetase (ProRS) to cause intracellular accumulation of uncharged tRNA. (nih.gov)
  • subunits
  • Endogenous eEF2, the 40 and 60 S ribosomal subunits, and total tRNAs were purified from HeLa cells (Fig. 4). (nih.gov)
  • While the structure of the catalytic HisGS subunit is related to the catalytic domain of another family of (HisGL)2 ATP phosphoribosyl transferases that is functional in the absence of additional regulatory subunits, the structure of the regulatory HisZ subunit is distantly related to class II aminoacyl-tRNA synthetases. (uni-regensburg.de)
  • interacts
  • HF interacts with both the site for amino acid activation and the site for docking the 3′-end of tRNAa, Thermal melting19 of ProRS in the presence of different ligands. (nih.gov)
  • structure
  • A general structure of an aminoacyl-tRNA synthetase is shown here with an editing site as well as an activation site. (wikipedia.org)
  • Here we report an unusual 2.0 Å structure showing that ATP directly locks onto and orients two parts of HF onto human ProRS, so that one part of HF mimics bound proline and the other mimics the 3' end of bound tRNA. (nih.gov)