β-sheet and a six-stranded outer β-sheet . This protein fold was a new fold observed for a cytochrome. Both individual crystal structures provided mechanistic insights. The DH domain was soaked with the inhibitor cellobionolactam which resolved the binding position of the substrate and gave a mechanistic explanation for the reductive half-reaction [52]. The CYT domain structure revealed an unusual axial haem b iron coordination by a His and a Met residue, which is the basis for intramolecular electron transfer between the two domains. A mutational study on the iron-coordinating haem ligands performed by Rotseart et al. showed that either the replacement of Met by His, or the switching of both ligands resulted in an IET inactive CYT domain. In 2015, the elucidation of the full-length structures of CDH from Crassicarpon hotsonii (syn. Myriococcum thermophilum) (PDB ID: 4QI6) and Neurospora crassa (PDB ID: 4QI7) increased the understanding of the domain mobility for the role of CYT as built-in redox mediator. Tan and Kracher et al. showed that CDH exists in a closed-state and an open-state conformation. In the closed-state the haem b accepts an electron from the FAD after substrate oxidation and it donates the electron to an external electron acceptor in the open-state. It was found that IET does not depend on the prominent Trp residue positioned directly between the FAD and the haem cofactor, but on a surface exposed Arg in the substrate channel, which stabilises the interaction with CYT through a haem propionate group. The heme b propionate-D is folded away, and a hydrogen bond to Tyr99 in the CYT domain prevents it from interacting directly with the DH active site. The closest edge-to-edge distance between heme b and FAD is 9 Å, which is well within the 14-Å limit for efficient electron transfer. The mobile CYT domain of CDH is a unique feature among GMC-oxidoreductases and acquired at a later stage of evolution. The CYT domain mobility is regulated by a flexible peptide linker of varying length and composition (e.g., N. crassa CDH IIA = 17 amino acids, N. crassa CDH IIB = 33 amino acids), which connects both domains. The movement of CYT has been observed by AFM and SAXS studies. Phylogenetic classification The CDH sequences evolved into four phylogenetic branches: Class I CDH sequences are found exclusively in Basidiomycota whereas CDH sequences from Class II, Class III, and Class IV are found only in Ascomycota.