3HFV
Crystal structure of human mitochondrial phenylalanyl-tRNA synthetase complexed with m-tyrosine
Summary for 3HFV
| Entry DOI | 10.2210/pdb3hfv/pdb |
| Related | 3CMQ |
| Descriptor | Phenylalanyl-tRNA synthetase, mitochondrial, META-TYROSINE (3 entities in total) |
| Functional Keywords | classii aarss fold, rrm domain, trna, rna recogntion, aminoacyl-trna synthetase, atp-binding, ligase, mitochondrion, nucleotide-binding, protein biosynthesis, transit peptide, m-tyrosine, polymorphism |
| Biological source | Homo sapiens (human) |
| Total number of polymer chains | 1 |
| Total formula weight | 48687.23 |
| Authors | Klipcan, L.,Moor, N.,Kessler, N.,Safro, M.G. (deposition date: 2009-05-12, 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 Cited by 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: 19549855DOI: 10.1073/pnas.0905212106 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.6 Å) |
Structure validation
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