Escherichia coli TehB requires S-adenosylmethionine as a cofactor to mediate tellurite resistance

The Escherichia coli chromosomal determinant for tellurite resistance consi sts of two genes (tehA and tehB) which, when expressed on a multicopy plasm id, confer resistance to K2TeO3 at 128 mug/ml, compared to the MIC of 2 mug /ml for the wild type. TehB is a cytoplasmic protein which possesses three conserved motifs (I, II, and III) found in S-adenosyl-L-methionine (SAM)-de pendent non-nucleic acid methyltransferases. Replacement of the conserved a spartate residue in motif I by asparagine or alanine, or of the conserved p henylalanine in motif II by tyrosine or alanine, decreased resistance to ba ckground levels. Our results are consistent with motifs I and II in TehB be ing involved in SAM binding. Additionally, conformational changes in TehB a re observed upon binding of both tellurite and SAM. The hydrodynamic radius of TehB measured by dynamic light scattering showed a similar to 20% decre ase upon binding of both tellurite and SAM. These data suggest that TehB ut ilizes a methyltransferase activity in the detoxification of tellurite.