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| | <StructureSection load='5m58' size='340' side='right'caption='[[5m58]], [[Resolution|resolution]] 2.05Å' scene=''> | | <StructureSection load='5m58' size='340' side='right'caption='[[5m58]], [[Resolution|resolution]] 2.05Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5m58]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/'streptomyces_hazeliensis' 'streptomyces hazeliensis']. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5M58 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5M58 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5m58]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Streptomyces_rishiriensis Streptomyces rishiriensis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5M58 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5M58 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=SAH:S-ADENOSYL-L-HOMOCYSTEINE'>SAH</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.05Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">couO ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=68264 'Streptomyces hazeliensis'])</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SAH:S-ADENOSYL-L-HOMOCYSTEINE'>SAH</scene></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5m58 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5m58 OCA], [http://pdbe.org/5m58 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5m58 RCSB], [http://www.ebi.ac.uk/pdbsum/5m58 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5m58 ProSAT]</span></td></tr> | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5m58 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5m58 OCA], [https://pdbe.org/5m58 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5m58 RCSB], [https://www.ebi.ac.uk/pdbsum/5m58 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5m58 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/COUO_STRRH COUO_STRRH]] Mediates C-methylation at the 8-position of the aminocoumarin moieties in coumermycin A1 in the biosynthetic pathway of coumermycin antibiotic. Active on both mono- and bis-amides for mono- and di-C-methylation adjacent to the phenolic hydroxyl before it is glycosylated by CouM.<ref>PMID:16274243</ref> | + | [https://www.uniprot.org/uniprot/COUO_STRRH COUO_STRRH] Mediates C-methylation at the 8-position of the aminocoumarin moieties in coumermycin A1 in the biosynthetic pathway of coumermycin antibiotic. Active on both mono- and bis-amides for mono- and di-C-methylation adjacent to the phenolic hydroxyl before it is glycosylated by CouM.<ref>PMID:16274243</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Streptomyces hazeliensis]] | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Gruber, K]] | + | [[Category: Streptomyces rishiriensis]] |
| - | [[Category: Pavkov-Keller, T]] | + | [[Category: Gruber K]] |
| - | [[Category: C-methyltransferase]] | + | [[Category: Pavkov-Keller T]] |
| - | [[Category: Couo]]
| + | |
| - | [[Category: Friedel-craft alkylation]]
| + | |
| - | [[Category: Sam]]
| + | |
| - | [[Category: Transferase]]
| + | |
| - | [[Category: Transfrease]]
| + | |
| Structural highlights
Function
COUO_STRRH Mediates C-methylation at the 8-position of the aminocoumarin moieties in coumermycin A1 in the biosynthetic pathway of coumermycin antibiotic. Active on both mono- and bis-amides for mono- and di-C-methylation adjacent to the phenolic hydroxyl before it is glycosylated by CouM.[1]
Publication Abstract from PubMed
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.
Crystal Structure and Catalytic Mechanism of CouO, a Versatile C-Methyltransferase from Streptomyces rishiriensis.,Pavkov-Keller T, Steiner K, Faber M, Tengg M, Schwab H, Gruber-Khadjawi M, Gruber K PLoS One. 2017 Feb 2;12(2):e0171056. doi: 10.1371/journal.pone.0171056., eCollection 2017. PMID:28152088[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Pacholec M, Tao J, Walsh CT. CouO and NovO: C-methyltransferases for tailoring the aminocoumarin scaffold in coumermycin and novobiocin antibiotic biosynthesis. Biochemistry. 2005 Nov 15;44(45):14969-76. PMID:16274243 doi:http://dx.doi.org/10.1021/bi051599o
- ↑ 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. 2017 Feb 2;12(2):e0171056. doi: 10.1371/journal.pone.0171056., eCollection 2017. PMID:28152088 doi:http://dx.doi.org/10.1371/journal.pone.0171056
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