ANGIOGENIC TYROSYL TRNA SYNTHETASE COMPOSITIONS AND METHODS

摘要

The present invention provides an isolated tyrosyl tRNA synthetase (TyrRS)polypeptide variant which comprises (a) a Rossmann fold region or a portionthereof, preferably including an 5 coil; and (b) an anticodon recognitiondomain or portion thereof, preferably including an 14 coil. Preferably, the 5coil and the 14 coil have a greater spatial separation in the tertiarystructure of the variant compared to the corresponding spatial separation innative human TyrRS. The variant preferably comprises an amino acid residuesequence identity of at least about 50 % compared to the amino acid residuesequence of human TyrRS (SEQ ID NO: 3), includes at least one non-conservativeamino acid residue substitution relative to the amino acid residue sequence ofhuman TyrRS, and preferably presents an exposed ELR motif in the 5 coil on anexternal portion of the tertiary structure of the polypeptide. A preferredTyrRS protein variant comprises the amino acid residue sequence of SEQ ID NO:4 or a portion thereof. The proteins and protein fragments of the inventionare angiogenic and are useful for stimulating angiogenesis in mammaliantissues.