title: The structure of Rv2372c identifies an RsmE-like methyltransferase from Mycobacterium 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 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 (1487)16S rRNA(1510) helps to identify binding pockets for SAM (in the deep trefoil knot) and substrate RNA (at the dimer interface) and suggests an S(N)2 mechanism for the methylation of N3 of U1498 in 16S rRNA.
authors.affiliation: Structural Biology Unit, CSIR - Institute of Genomics and Integrative Biology, Mathura Road, New Delhi 110 020, India.
authors.forename: Atul
authors.initials: A
authors.lastname: Kumar
authors.affiliation: Structural Biology Unit, CSIR - Institute of Genomics and Integrative Biology, Mathura Road, New Delhi 110 020, India.
authors.forename: Santosh
authors.initials: S
authors.lastname: Kumar
authors.affiliation: Structural Biology Unit, CSIR - Institute of Genomics and Integrative Biology, Mathura Road, New Delhi 110 020, India.
authors.forename: Bhupesh
authors.initials: B
authors.lastname: Taneja
mesh_terms: D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics; D003460:Crystallization; D018360:Crystallography, X-Ray; D029968:Escherichia coli Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000235:genetics; D005816:Genetic Complementation Test; D008780:Methyltransferases / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000235:genetics; D008969:Molecular Sequence Data; D009169:Mycobacterium tuberculosis / Q000201:enzymology* / Q000235:genetics; D055503:Protein Multimerization / Q000235:genetics; D012336:RNA, Ribosomal, 16S / Q000737:chemistry / Q000235:genetics; D017384:Sequence Deletion / Q000235:genetics; D040681:Structural Homology, Protein
chemical_list: D001426:Bacterial Proteins; D029968:Escherichia coli Proteins; D012336:RNA, Ribosomal, 16S; D008780:Methyltransferases; C525730:RsmE protein, E coli
keywords: Mycobacterium tuberculosis; RNA methyltransferases; RsmE; Rv2372c; SN2 mechanism; SPOUT superfamily