Class I CDHs have a strong affinity for cellulose and bind presumably via a cellulose binding-site on the surface of the DH domain that is different from the active-site. This cellulose binding-site is not present in other CDH classes. The binding to cellulose in Class II CDHs depends on the presence of a C-terminal family 1 carbohydrate binding module (CBM1). Some Class II CDH feature a C-terminal CBM1 and are classified as Class IIA CDHs, whereas Class IIB CDHs have no CBM1 and do not bind to cellulose. Other differences between Class I and Class II CDHs are in their substrate specificity and the pH optimum of the IET. Little can be said about Class III and Class IV CDHs, which have not yet been expressed and characterised. From sequence alignments a different active-site geometry can be deduced, but the substrate is unknown. Class IV CDHs are evolutionary furthest related to the other CDH classes and do not feature an electron transferring CYT domain, which suggests a different physiological role and the loss of its ability for DET. Catalysis CDH catalyses the 2e-/2H+ oxidation of the anomeric carbon atom (C1) of the disaccharide cellobiose to the cellobiono-δ-lactone hydrolyses further to cellobionic acid in water. Besides the natural substrate cellobiose and the cellodextrins cellotriose, cellotetraose, cellopentaose, and cellohexaose also the cellulose building unit glucose, as well as the hemicellulose building monomers or breakdown products galactose, mannose, mannobiose, mannopentaose, xylose, xylobiose and xylotriose, or starch derived maltose, maltotriose and maltotetraose have been reported as substrates of greatly varying catalytic efficiency for CDH. A very good substrate not related to plant polysaccharides is lactose, because of its structural similarity to cellobiose. Cellobiose, cello-oligosaccharides, and lactose are the substrates for which CDH exhibits the highest catalytic efficiency, whereas monosaccharides are bad substrates with a very low affinity (high KM) to only the catalytic C-site of CDH. The extreme discrepancy of the catalytic efficiencies of P. chrysosporium CDH for cellobiose over glucose (87500 : 1) is been connected to the physiological role of the white-rot basidiomycete enzyme. In ascomycete CDHs the discrimination of glucose is less strict and a wider spectrum of mono- and oligosaccharides are converted. Of course, the affinity of CDH to di- and oligosaccharide substrates is much higher than for monosaccharides. However, Class II CDHs have KM-values for glucose of 10–100 mM, which is in the range of FAD-dependent glucose oxidase, also