Prof. Mark Safro

The William and Lee Abramowitz Professorial Chair in Molecular Biophysics

Tel: (972)-8-934-3320;
Fax: (972)-8-934-4136;

Scientific Activities

Aminoacyl-tRNA synthetases (aaRSs) are unique amongst the thousands and thousands proteins within the living cell in that they are located at the cross-road where come together to a focus the interests of genetic code translation, origin of life, RNA-protein interactions, RNA splicing, amino acid biosynthesis, proofreading activity, signal transduction pathways and new antiinfectives drug targets. The aaRSs are responsible for the aminoacylation of cognate tRNA with their corresponding amino acids, key step in protein biosynthesis. The attachment of the correct amino acid to a tRNA by aaRS determines the accuracy of the translation of the genetic code. For this reason the aaRS should be highly selective as well as discriminative. We are currently concentrating on revealing of similarity and distinctions between prokaryotic and eukaryotic Phenylalanyl-tRNA synthetases. Modes of interactions with substrate tRNA Phe appear to be different in both systems. We are also studying the mechanism whereby fidelity of the genetic code translation in aaRSs is maintained. While aaRSs have developed mechanisms to prevent the incorporation of wrong natural amino acids into the polypeptide chains, their fidelity declines in the face of unnatural analogs. The understanding of activation mechanism of unnatural amino acids and plasticity limits of aaRSs active site is correlated to the production of proteins with new physical properties.

X-Ray 1.  X-Ray analysis of phenylalanyl-tRNA synthetase from Thermus thermophilus complexed with tRNA and other functional ligands.
Aminoacyl-tRNA 2. Aminoacyl-tRNA synthetases and disease.
The aaRSs-tRNA encounter 3. The aaRSs-tRNA encounter complexes and electrostatic interactions.
Amino acid biogenesis 4. Amino acid biogenesis, evolution of the genetic code and aminoacyl-tRNA synthetases
Amino acid biogenesis 5. The structure of Human Mitochondrial Phenylalanyl-tRNA Synthetase