3HFZ

Crystal structure of Thermus thermophilus Phenylalanyl-tRNA synthetase complexed with m-tyrosine

Summary for 3HFZ

• Entry DOI: 10.2210/pdb3hfz/pdb
• Related: 1cmq 1pys
• Descriptor: Phenylalanyl-tRNA synthetase alpha chain, Phenylalanyl-tRNA synthetase beta chain, META-TYROSINE, ... (4 entities in total)
• Functional Keywords: heterodimer, phenylalanyl-trna, thermus thermophilus, trna, m-tyrosine, aminoacyl-trna synthetase, atp-binding, ligase, magnesium, metal-binding, nucleotide-binding, protein biosynthesis, rna-binding, trna-binding
• Biological source: Thermus thermophilus; More
• Cellular location: Cytoplasm: P27001 P27002
• Total number of polymer chains: 2
• Total formula weight: 126392.23

Authors

Klipcan, L.,Moor, N.,Kessler, N.,Safro, M.G. (deposition date: 2009-05-13, release date: 2009-07-21, Last modification date: 2023-09-06)

Primary citation

Klipcan, L.,Moor, N.,Kessler, N.,Safro, M.G.
Eukaryotic cytosolic and mitochondrial phenylalanyl-tRNA synthetases catalyze the charging of tRNA with the meta-tyrosine
Proc.Natl.Acad.Sci.USA, 106:11045-11048, 2009

PubMed Abstract: 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: m-tyrosine (m-Tyr), o-tyrosine (o-Tyr), and the standard p-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 (HsmtPheRS and HsctPheRS, respectively) catalyze direct attachment of m-Tyr to tRNA(Phe), 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 m-Tyr reveal the net of highly specific interactions within the synthetic and editing sites.

PubMed: 19549855
DOI: 10.1073/pnas.0905212106

Experimental method

X-RAY DIFFRACTION (2.9 Å)