Species-specific differences in the regulation of the aminoacylation activity of mammalian tryptophanyl-tRNA synthetases

Tryptophanyl-tRNA synthetases (TrpRSs) catalyze the aminoacylation of tRNATrp. Previously, I demonstrated that Zn2+-depleted human TrpRS is enzymatically inactive and that binding of Zn2+ or heme to human TrpRS stimulates its aminoacylation activity. In the present study, bovine and mouse TrpRSs were found to be constitutively active regardless of the presence of Zn2+ or ferriprotoporphyrin IX chloride. Mutagenesis experiments demonstrated that the human H130R mutant is constitutively active and that the bovine R135H, E438A double mutant binds with Zn2+ or heme to enhance its aminoacylation activity as does human wild-type TrpRS. These results provide the first evidence of species-specific regulation of TrpRS activity.