5M58

Crystal structure of CouO, a C-methyltransferase from Streptomyces rishiriensis

Summary for 5M58

• Entry DOI: 10.2210/pdb5m58/pdb
• Descriptor: C-methyltransferase CouO, S-ADENOSYL-L-HOMOCYSTEINE (3 entities in total)
• Functional Keywords: c-methyltransferase, couo, friedel-craft alkylation, sam, transfrease, transferase
• Biological source: Streptomyces rishiriensis
• Total number of polymer chains: 2
• Total formula weight: 52128.94

Authors

Pavkov-Keller, T.,Gruber, K. (deposition date: 2016-10-20, release date: 2017-02-15, Last modification date: 2024-05-08)

Primary citation

Pavkov-Keller, T.,Steiner, K.,Faber, M.,Tengg, M.,Schwab, H.,Gruber-Khadjawi, M.,Gruber, K.
Crystal Structure and Catalytic Mechanism of CouO, a Versatile C-Methyltransferase from Streptomyces rishiriensis.
PLoS ONE, 12:e0171056-e0171056, 2017

PubMed Abstract: Friedel-Crafts alkylation of aromatic systems is a classic reaction in organic chemistry, for which regiospecific mono-alkylation, however, is generally difficult to achieve. In nature, methyltransferases catalyze the addition of methyl groups to a wide range of biomolecules thereby modulating the physico-chemical properties of these compounds. Specifically, S-adenosyl-L-methionine dependent C-methyltransferases possess a high potential to serve as biocatalysts in environmentally benign organic syntheses. Here, we report on the high resolution crystal structure of CouO, a C-methyltransferase from Streptomyces rishiriensis involved in the biosynthesis of the antibiotic coumermycin A1. Through molecular docking calculations, site-directed mutagenesis and the comparison with homologous enzymes we identified His120 and Arg121 as key functional residues for the enzymatic activity of this group of C-methyltransferases. The elucidation of the atomic structure and the insight into the catalytic mechanism provide the basis for the (semi)-rational engineering of the enzyme in order to increase the substrate scope as well as to facilitate the acceptance of SAM-analogues as alternative cofactors.

PubMed: 28152088
DOI: 10.1371/journal.pone.0171056

Experimental method

X-RAY DIFFRACTION (2.05 Å)