4QI5

Dehydrogenase domain of Myriococcum thermophilum cellobiose dehydrogenase with bound cellobionolactam, MtDH

Summary for 4QI5

• Entry DOI: 10.2210/pdb4qi5/pdb
• Related: 4QI3 4QI4 4QI6 4QI7 4QI8
• Descriptor: Cellobiose dehydrogenase, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, FLAVIN-ADENINE DINUCLEOTIDE, ... (6 entities in total)
• Functional Keywords: fad/nad(p)-binding domain, cellobiose oxidizing, electron transfer, lignocellulose degradation, cdh cytochrome domain, cellobiose, cellobionolactam, oxidoreductase
• Biological source: Myriococcum thermophilum
• Total number of polymer chains: 1
• Total formula weight: 65429.84

Authors

Tan, T.C.,Gandini, R.,Sygmund, C.,Kittl, R.,Haltrich, D.,Ludwig, R.,Hallberg, B.M.,Divne, C. (deposition date: 2014-05-30, release date: 2015-07-15, Last modification date: 2024-11-20)

Primary citation

Tan, T.C.,Kracher, D.,Gandini, R.,Sygmund, C.,Kittl, R.,Haltrich, D.,Hallberg, B.M.,Ludwig, R.,Divne, C.
Structural basis for cellobiose dehydrogenase action during oxidative cellulose degradation.
Nat Commun, 6:7542-7542, 2015

PubMed 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.

PubMed: 26151670
DOI: 10.1038/ncomms8542

Experimental method

X-RAY DIFFRACTION (2.4 Å)