The structure of Rv2372c identifies an RsmE-like methyltransferase from Mycobacterium tuberculosis

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 from Mycobacterium tuberculosis has been identified as an RsmE-like methyltransferase which specifically methylates U1498 of 16S rRNA at the N3 position and can complement RsmE-deleted Escherichia 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 cofactor S-adenosylmethionine (SAM) and the 16S rRNA fragment ¹⁴⁸⁷16S rRNA¹⁵¹⁰ helps to identify binding pockets for SAM (in the deep trefoil knot) and substrate RNA (at the dimer interface) and suggests an S_N2 mechanism for the methylation of N3 of U1498 in 16S rRNA.