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Nat Commun. 2015 Jul 7;6:7542. doi: 10.1038/ncomms8542.

Structural basis for cellobiose dehydrogenase action during oxidative cellulose degradation.

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1] School of Biotechnology, KTH Royal Institute of Technology, AlbaNova University Center, Roslagstullsbacken 21, Stockholm S-10691, Sweden [2] Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Scheelelaboratoriet, Scheeles väg 2, Stockholm S-17177, Sweden.
Food Biotechnology Laboratory, Department of Food Science and Technology, Vienna Institute of Biotechnology (VIBT), BOKU-University of Natural Resources and Life Sciences, Muthgasse 18, Vienna A-1190, Austria.
1] Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm S-17177, Sweden [2] European Molecular Biology Laboratory, Hamburg Unit, Hamburg 22603, Germany; and Centre for Structural Systems Biology (CSSB), DESY-Campus, Hamburg 22603, Germany.


A new paradigm for cellulose depolymerization by fungi focuses on an oxidative mechanism involving cellobiose dehydrogenases (CDH) and copper-dependent lytic polysaccharide monooxygenases (LPMO); however, mechanistic studies have been hampered by the lack of structural information regarding CDH. CDH contains a haem-binding cytochrome (CYT) connected via a flexible linker to a flavin-dependent dehydrogenase (DH). Electrons are generated from cellobiose oxidation catalysed by DH and shuttled via CYT to LPMO. Here we present structural analyses that provide a comprehensive picture of CDH conformers, which govern the electron transfer between redox centres. Using structure-based site-directed mutagenesis, rapid kinetics analysis and molecular docking, we demonstrate that flavin-to-haem interdomain electron transfer (IET) is enabled by a haem propionate group and that rapid IET requires a closed CDH state in which the propionate is tightly enfolded by DH. Following haem reduction, CYT reduces LPMO to initiate oxygen activation at the copper centre and subsequent cellulose depolymerization.

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