Structural and biochemical characterization of an O-methyltransferase from Mycobacterium tuberculosis

Abstract

Rv0187c, a putative O-methyltransferase belongs to the methyltransf_3 (or PF01596) and classified class I OMT. This O-methyltransferase (O-MT) family transfer a methyl group (-CH3) to catechol-like substrates using S-adenosyl-L-methionine (SAM) as a methyl donor in a divalent metal ion dependent manner. Some of the Class I OMTs are well characterized and known to involve in many cellular processes such as secondary metabolism, antibiotics production and serve as modification tools of nucleotides. However, the exact biological function of other OMTs in this class, especially bacterial OMTs, remains elusive and these OMTs have a promiscuous specificity to their in-vitro substrates. Because each OMT has been described that have a unique chemistry corresponding to insertion loops in the vicinity of the active sites responsible for the substrate specificity, one possible explanation for this promiscuity is structural and sequence difference in respective insertion loops and the presence or absence of N-terminal region intervening active sites rather than conserved C-terminal regions that sustain the overall structure. Here, the crystal structures of Rv0187 from Mycobacterium tuberculosis H37Rv were determined in and co-factor bound form at resolutions of 2.08Å and 1.64 Å respectively. The overall structures of Rv0187 are similar with typical SAM-dependent methyltransferases sustained by the conserved C-terminal domain but have an insertion loop that is not homologous to the OMTs. Therefore, comparing functional and structural properties of Rv0187 with previously studied other O-MTs is the meaningful process in elucidating the biological function of this class of OMTs and valuable insight to further investigation.