6jcl
Crystal structure of cofactor-bound Rv0187 from MTB
Structural highlights
FunctionCAMT_MYCTU Catechol O-methyltransferase that can use various catechol-like compounds such as gallic acid (GA), 3,4-dihydroxy-5-methoxy-benzoic acid (5OMeBA), protocatechuic acid (PCA), 3,4-dihydroxy-benzaldehyde (DHA), dopamine, caffeic acid (CA), luteolin, quercetin, and 5-hydroxyuridine.[1] Publication Abstract from PubMedCatechol O-methyltransferase (COMT) is widely distributed in nature and installs a methyl group onto one of the vicinal hydroxyl groups of a catechol derivative. Enzymes belonging to this family require two cofactors for methyl transfer: S-adenosyl-l-methionine as a methyl donor and a divalent metal cation for regiospecific binding and activation of a substrate. We have determined two high-resolution crystal structures of Rv0187, one of three COMT paralogs from Mycobacterium tuberculosis, in the presence and absence of cofactors. The cofactor-bound structure clearly locates strontium ions and S-adenosyl-l-homocysteine in the active site, and together with the complementary structure of the ligand-free form, it suggests conformational dynamics induced by the binding of cofactors. Examination of in vitro activities revealed promiscuous substrate specificity and relaxed regioselectivity against various catechol-like compounds. Unexpectedly, mutation of the proposed catalytic lysine residue did not abolish activity but altered the overall landscape of regiospecific methylation. Structural and biochemical characterization of Rv0187, an O-methyltransferase from Mycobacterium tuberculosis.,Lee S, Kang J, Kim J Sci Rep. 2019 May 30;9(1):8059. doi: 10.1038/s41598-019-44592-7. PMID:31147608[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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