Structural studies of lysyl-tRNA synthetase: Conformational changes induced by substrate binding?

Lysyl-tRNA synthetase is a member of the class II aminoacyl-tRNA synthetase s and catalyses the specific aminoacylation of tRNA(Lys). The crystal struc ture of The constitutive lysyl-tRNA synthetase (LysS) from Escherichia coli has been determined to 2.7 Angstrom resolution in the unliganded form and in a complex with the lysine substrate. A comparison between the unliganded and lysine-bound structures reveals major conformational changes upon lysi ne binding. The lysine substrate is involved in a network of hydrogen bonds . Two of these interactions, one between the cr-amino group and the carbony l oxygen of Gly 216 and the other between the carboxylate group and the sid e chain of Arg 262, trigger a subtle and complicated reorganization of the active site, involving the ordering of two loops (residues 215-217 and 444- 455), a change in conformation of residues 393-409, and a rotation of a 4-h elix bundle domain (located between motif 2 and 3) by 10 degrees. The resul t of these changes is a closing up of the active site upon lysine binding.