Structural Studies of Lysyl-tRNA Synthetase:  Conformational Changes Induced by Substrate Binding

Lysyl-tRNA synthetase is a member of the class II aminoacyl-tRNA synthetases and catalyses the specific aminoacylation of tRNALys. The crystal structure of the constitutive lysyl-tRNA synthetase (LysS) from Escherichia coli has been determined to 2.7 Å 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 lysine binding. The lysine substrate is involved in a network of hydrogen bonds. Two of these interactions, one between the α-amino group and the carbonyl oxygen of Gly 216 and the other between the carboxylate group and the side 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-helix bundle domain (located between motif 2 and 3) by 10°. The result of these changes is a closing up of the active site upon lysine binding.