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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.

Author information

1
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.
2
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.
3
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.

Abstract

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.

PMID:
26151670
PMCID:
PMC4507011
DOI:
10.1038/ncomms8542
[Indexed for MEDLINE]
Free PMC Article

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