Structural and functional basis of C-methylation of coumarin scaffolds by NovO
Sadler, Joanna C. and Chung, Chun-wa H. and Mosley, Julie E. and Burley, Glenn A. and Humphreys, Luke D. (2017) Structural and functional basis of C-methylation of coumarin scaffolds by NovO. ACS Chemical Biology, 12 (2). pp. 374-379. ISSN 1554-8937 (https://doi.org/10.1021/acschembio.6b01053)
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Abstract
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.
ORCID iDs
Sadler, Joanna C. ORCID: https://orcid.org/0000-0002-8442-0760, Chung, Chun-wa H., Mosley, Julie E., Burley, Glenn A. and Humphreys, Luke D.;-
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Item type: Article ID code: 60153 Dates: DateEvent17 February 2017Published9 January 2017Published Online9 January 2017AcceptedNotes: This document is the Accepted Manuscript version of a Published Work that appeared in final form in ACS Chemical Biology, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see http://dx.doi.org/10.1021/acschembio.6b01053. Subjects: Science > Chemistry Department: Faculty of Science > Pure and Applied Chemistry
Technology and Innovation Centre > BionanotechnologyDepositing user: Pure Administrator Date deposited: 13 Mar 2017 12:53 Last modified: 04 Dec 2024 01:18 URI: https://strathprints.strath.ac.uk/id/eprint/60153