Crystal Structure and Catalytic Mechanism of CouO, a Versatile C-Methyltransferase from Streptomyces rishiriensis.
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 p...
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Public Library of Science (PLoS)
2017-01-01
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| Series: | PLoS ONE |
| Online Access: | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0171056&type=printable |
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| author | Tea Pavkov-Keller Kerstin Steiner Mario Faber Martin Tengg Helmut Schwab Mandana Gruber-Khadjawi Karl Gruber |
| author_facet | Tea Pavkov-Keller Kerstin Steiner Mario Faber Martin Tengg Helmut Schwab Mandana Gruber-Khadjawi Karl Gruber |
| author_sort | Tea Pavkov-Keller |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-9fad6ec7b63d4975b0e90a7b5e97f40b |
| institution | Kabale University |
| issn | 1932-6203 |
| language | English |
| publishDate | 2017-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj-art-9fad6ec7b63d4975b0e90a7b5e97f40b2025-08-20T03:24:29ZengPublic Library of Science (PLoS)PLoS ONE1932-62032017-01-01122e017105610.1371/journal.pone.0171056Crystal Structure and Catalytic Mechanism of CouO, a Versatile C-Methyltransferase from Streptomyces rishiriensis.Tea Pavkov-KellerKerstin SteinerMario FaberMartin TenggHelmut SchwabMandana Gruber-KhadjawiKarl GruberFriedel-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.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0171056&type=printable |
| spellingShingle | Tea Pavkov-Keller Kerstin Steiner Mario Faber Martin Tengg Helmut Schwab Mandana Gruber-Khadjawi Karl Gruber Crystal Structure and Catalytic Mechanism of CouO, a Versatile C-Methyltransferase from Streptomyces rishiriensis. PLoS ONE |
| title | Crystal Structure and Catalytic Mechanism of CouO, a Versatile C-Methyltransferase from Streptomyces rishiriensis. |
| title_full | Crystal Structure and Catalytic Mechanism of CouO, a Versatile C-Methyltransferase from Streptomyces rishiriensis. |
| title_fullStr | Crystal Structure and Catalytic Mechanism of CouO, a Versatile C-Methyltransferase from Streptomyces rishiriensis. |
| title_full_unstemmed | Crystal Structure and Catalytic Mechanism of CouO, a Versatile C-Methyltransferase from Streptomyces rishiriensis. |
| title_short | Crystal Structure and Catalytic Mechanism of CouO, a Versatile C-Methyltransferase from Streptomyces rishiriensis. |
| title_sort | crystal structure and catalytic mechanism of couo a versatile c methyltransferase from streptomyces rishiriensis |
| url | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0171056&type=printable |
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