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| | <StructureSection load='5mgz' size='340' side='right'caption='[[5mgz]], [[Resolution|resolution]] 1.90Å' scene=''> | | <StructureSection load='5mgz' size='340' side='right'caption='[[5mgz]], [[Resolution|resolution]] 1.90Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5mgz]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/As_4.1832_[[streptomyces_laceyi]] As 4.1832 [[streptomyces laceyi]]]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5MGZ OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5MGZ FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5mgz]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Streptomyces_niveus Streptomyces niveus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5MGZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5MGZ FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <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]] 1.9Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">novO ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=193462 AS 4.1832 [[Streptomyces laceyi]]])</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SAH:S-ADENOSYL-L-HOMOCYSTEINE'>SAH</scene></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/8-demethylnovobiocic_acid_C(8)-methyltransferase 8-demethylnovobiocic acid C(8)-methyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.1.1.284 2.1.1.284] </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=5mgz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5mgz OCA], [https://pdbe.org/5mgz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5mgz RCSB], [https://www.ebi.ac.uk/pdbsum/5mgz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5mgz ProSAT]</span></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=5mgz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5mgz OCA], [http://pdbe.org/5mgz PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5mgz RCSB], [http://www.ebi.ac.uk/pdbsum/5mgz PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5mgz ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/NOVO_STRNV NOVO_STRNV]] C-methyltransferase that methylates 8-demethylnovobiocic acid to produce novobiocic acid in the novobiocin biosynthesis pathway. Novobiocin is an aminocoumarin family antibiotic that targets bacterial DNA gyrases.<ref>PMID:16274243</ref> | + | [https://www.uniprot.org/uniprot/NOVO_STRNV NOVO_STRNV] C-methyltransferase that methylates 8-demethylnovobiocic acid to produce novobiocic acid in the novobiocin biosynthesis pathway. Novobiocin is an aminocoumarin family antibiotic that targets bacterial DNA gyrases.<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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| | </StructureSection> | | </StructureSection> |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Chung, C W]] | + | [[Category: Streptomyces niveus]] |
| - | [[Category: Mosley, J]] | + | [[Category: Chung C-W]] |
| - | [[Category: Sadler, J C]] | + | [[Category: Mosley J]] |
| - | [[Category: C methyltransferase]] | + | [[Category: Sadler JC]] |
| - | [[Category: Novobiocin biosynthesis]]
| + | |
| - | [[Category: Sam dependent]]
| + | |
| - | [[Category: Transferase]]
| + | |
| Structural highlights
Function
NOVO_STRNV C-methyltransferase that methylates 8-demethylnovobiocic acid to produce novobiocic acid in the novobiocin biosynthesis pathway. Novobiocin is an aminocoumarin family antibiotic that targets bacterial DNA gyrases.[1]
Publication Abstract from PubMed
C-methylation of aromatic small molecules by C-methyltransferases (C-MTs) is an important biological transformation that involves C-C bond formation using S-adenosyl-l-methionine (SAM) as the methyl donor. Here, two advances in the mechanistic understanding of C-methylation of the 8-position of coumarin substrates catalyzed by the C-MT NovO from Streptomyces spheroides are described. First, a crystal structure of NovO reveals the Arg116-Asn117 and His120-Arg121 motifs are essential for coumarin substrate binding. Second, the active-site His120 is responsible for deprotonation of the phenolic 7-hydroxyl group on the coumarin substrate, activating the rate-determining methyl transfer step from SAM. This work expands our mechanistic knowledge of C-MTs, which could be used in the downstream development of engineered biocatalysts for small molecule C-alkylations.
Structural and Functional Basis of C-Methylation of Coumarin Scaffolds by NovO.,Sadler JC, Chung CH, Mosley JE, Burley GA, Humphreys LD ACS Chem Biol. 2017 Jan 13. doi: 10.1021/acschembio.6b01053. PMID:28068060[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
- ↑ Sadler JC, Chung CH, Mosley JE, Burley GA, Humphreys LD. Structural and Functional Basis of C-Methylation of Coumarin Scaffolds by NovO. ACS Chem Biol. 2017 Jan 13. doi: 10.1021/acschembio.6b01053. PMID:28068060 doi:http://dx.doi.org/10.1021/acschembio.6b01053
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