The structure of Rv2372c identifies an RsmE-like methyltransferase fromMycobacterium tuberculosis

Abstract

U1498 of 16S rRNA plays an important role in translation fidelity as well as in antibiotic response. U1498 is present in a methylated form in the decoding centre of the ribosome. In this study, Rv2372c fromMycobacterium tuberculosishas been identified as an RsmE-like methyltransferase which specifically methylates U1498 of 16S rRNA at the N3 position and can complement RsmE-deletedEscherichia coli. The crystal structure of Rv2372c has been determined, and reveals that the protein belongs to a distinct class in the SPOUT superfamily and exists as a dimer. The deletion of critical residues at the C-terminus of Rv2372c leads to an inability of the protein to form stable dimers and to abolition of the methyltransferase activity. A ternary model of Rv2372c with its cofactorS-adenosylmethionine (SAM) and the 16S rRNA fragment148716S rRNA1510helps to identify binding pockets for SAM (in the deep trefoil knot) and substrate RNA (at the dimer interface) and suggests an SN2 mechanism for the methylation of N3 of U1498 in 16S rRNA.