5mgz
From Proteopedia
Streptomyces Spheroides NovO (8-demethylnovbiocic acid methyltransferase) with SAH
Structural highlights
FunctionNOVO_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 PubMedC-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
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