Beyond the Protein Matrix: Probing Cofactor Variants in a Baeyer-Villiger Oxygenation Reaction.
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Martinoli C, Dudek HM, Orru R, Edmondson DE, Fraaije MW, Mattevi A
Beyond the Protein Matrix: Probing Cofactor Variants in a Baeyer-Villiger Oxygenation Reaction.
ACS Catal. 2013;3(12):3058-3062.
- PubMed ID
- 24443704 [ View in PubMed]
- Abstract
A general question in biochemistry is the interplay between the chemical properties of cofactors and the surrounding protein matrix. Here, the functions of NADP+ and FAD are explored by investigation of a representative monooxygenase reconstituted with chemically-modified cofactor analogues. Like pieces of a jigsaw puzzle, the enzyme active site juxtaposes the flavin and nicotinamide rings, harnessing their H-bonding and steric properties to finely construct an oxygen-reacting center that restrains the flavin-peroxide intermediate in a catalytically-competent orientation. Strikingly, the regio- and stereoselectivities of the reaction are essentially unaffected by cofactor modifications. These observations indicate a remarkable robustness of this complex multi-cofactor active site, which has implications for enzyme design based on cofactor engineering approaches.