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Enzyme Activation with a Synthetic Catalytic Co‐enzyme Intermediate: Nucleotide Methylation by Flavoenzymes
Author(s) -
BouNader Charles,
Cornu David,
Guerineau Vincent,
Fogeron Thibault,
Fontecave Marc,
Hamdane Djemel
Publication year - 2017
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201706219
Subject(s) - enzyme , methylation , catalysis , chemistry , biochemistry , nucleotide , combinatorial chemistry , enzyme activator , gene
To facilitate production of functional enzymes and to study their mechanisms, especially in the complex cases of coenzyme‐dependent systems, activation of an inactive apoenzyme preparation with a catalytically competent coenzyme intermediate is an attractive strategy. This is illustrated with the simple chemical synthesis of a flavin‐methylene iminium compound previously proposed as a key intermediate in the catalytic cycle of several important flavoenzymes involved in nucleic acid metabolism. Reconstitution of both flavin‐dependent RNA methyltransferase and thymidylate synthase apoproteins with this synthetic compound led to active enzymes for the C5‐uracil methylation within their respective transfer RNA and dUMP substrate. This strategy is expected to be of general application in enzymology.