Download MendeleyBeyond the Protein Matrix: Probing Cofactor Variants in a Baeyer-Villiger Oxygenation Reaction.
Martinoli, C., Dudek, H.M., Orru, R., Edmondson, D.E., Fraaije, M.W., Mattevi, A.(2013) ACS Catal 3: 3058
- PubMed: 24443704
- DOI: https://doi.org/10.1021/cs400837z
- Primary Citation of Related Structures:
4C74, 4C77, 4OVI - 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.
Organizational Affiliation:
Department of Biology and Biotechnology, University of Pavia, Via Ferrata 9, 27100 Pavia, Italy.
