Beschreibung:
<jats:p>
The accumulation of proteins damaged by reactive oxygen species (ROS), conventionally regarded as having pathological potentials, is associated with age-related diseases such as Alzheimer's, atherosclerosis, and cataractogenesis. Exposure of the aromatic amino acid phenylalanine to ROS-generating systems produces multiple isomers of tyrosine:
<jats:italic>m</jats:italic>
-tyrosine (
<jats:italic>m</jats:italic>
-Tyr),
<jats:italic>o</jats:italic>
-tyrosine (
<jats:italic>o</jats:italic>
-Tyr), and the standard
<jats:italic>p</jats:italic>
-tyrosine (Tyr). Previously it was demonstrated that exogenously supplied, oxidized amino acids could be incorporated into bacterial and eukaryotic proteins. It is, therefore, likely that in many cases, in vivo-damaged amino acids are available for de novo synthesis of proteins. Although the involvement of aminoacyl-tRNA synthetases in this process has been hypothesized, the specific pathway by which ROS-damaged amino acids are incorporated into proteins remains unclear. We provide herein evidence that mitochondrial and cytoplasmic phenylalanyl-tRNA synthetases (
<jats:italic>Hsmt</jats:italic>
PheRS and
<jats:italic>Hsct</jats:italic>
PheRS, respectively) catalyze direct attachment of
<jats:italic>m</jats:italic>
-Tyr to tRNA
<jats:sup>Phe</jats:sup>
, thereby opening the way for delivery of the misacylated tRNA to the ribosome and incorporation of ROS-damaged amino acid into eukaryotic proteins. Crystal complexes of mitochondrial and bacterial PheRSs with
<jats:italic>m</jats:italic>
-Tyr reveal the net of highly specific interactions within the synthetic and editing sites.
</jats:p>