Crystal structure of the Legionella pneumophila Lpg2936 in complex with the cofactor S-adenosyl-L-methionine reveals novel insights into the mechanism of RsmE family methyltransferases.

ABSTRACT: The methylation of U1498 located in the 16S ribosomal RNA of Escherichia coli is an important modification affecting ribosomal activity. RsmE methyltransferases methylate specifically this position in a mechanism that requires an S-adenosyl-L-methionine (AdoMet) molecule as cofactor. Here we report the structure of Apo and AdoMet-bound Lpg2936 from Legionella pneumophila at 1.5 and 2.3 Å, respectively. The protein comprises an N-terminal PUA domain and a C-terminal SPOUT domain. The latter is responsible for protein dimerization and cofactor binding. Comparison with similar structures suggests that Lpg2936 is an RsmE-like enzyme that can target the equivalent of U1498 in the L. pneumophila ribosomal RNA, thereby potentially enhancing ribosomal activity during infection-mediated effector production. The multiple copies of the enzyme found in both structures reveal a flexible conformation of the bound AdoMet ligand. Isothermal titration calorimetry measurements suggest an asymmetric two site binding mode. Our results therefore also provide unprecedented insights into AdoMet/RsmE interaction, furthering our understanding of the RsmE catalytic mechanism.

SUBMITTER: Pinotsis N 

PROVIDER: S-EPMC5699498 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature