6JCL

Crystal structure of cofactor-bound Rv0187 from MTB

Summary for 6JCL

• Entry DOI: 10.2210/pdb6jcl/pdb
• Descriptor: Probable O-methyltransferase, S-ADENOSYL-L-HOMOCYSTEINE, STRONTIUM ION, ... (6 entities in total)
• Functional Keywords: methyltransferase, metal binding protein
• Biological source: Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)
• Total number of polymer chains: 8
• Total formula weight: 204351.88

Authors

Kim, J.,Lee, S. (deposition date: 2019-01-29, release date: 2019-12-11, Last modification date: 2023-11-22)

Primary citation

Lee, S.,Kang, J.,Kim, J.
Structural and biochemical characterization of Rv0187, an O-methyltransferase from Mycobacterium tuberculosis.
Sci Rep, 9:8059-8059, 2019

PubMed Abstract: Catechol 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.

PubMed: 31147608
DOI: 10.1038/s41598-019-44592-7

Experimental method

X-RAY DIFFRACTION (1.644 Å)