Crystal structure of Rv1220c, a SAM-dependentO-methyltransferase fromMycobacterium tuberculosis

Abstract

Rv1220c fromMycobacterium tuberculosisis annotated as anO-methyltransferase (MtbOMT). Currently, no structural information is available for this protein. Here, the crystal structure ofMtbOMT refined to 2.0 Å resolution is described. The structure reveals the presence of a methyltransferase fold and shows clear electron density for one molecule ofS-adenosylmethionine (SAM), which was apparently bound by the protein during its production inEscherichia coli. Although the overall structure ofMtbOMT resembles the structures ofO-methyltransferases fromCornybacterium glutamicum,Coxiella burnettiandAlfa alfa, differences are observed in the residues that make up the active site. Notably, substitution of Asp by His164 seems to abrogate metal binding byMtbOMT. A putative catalytic His–Asp pair located in the vicinity of SAM is absolutely conserved inMtbOMT homologues from all species ofMycobacterium, suggesting a conserved function for this protein.