Different folds in endoglucanases with the catalytic residues highlighted in inset. (A) (α/β)8 fold (Acidothermus cellulolyticus pdb id: 1ece) (B) β-jelly roll fold (Streptomyces lividans pdb id: 2nlr), and (C) (α/α)6 fold (Clostridium thermocellum F7 pdb id: 1l1y) are shown in cartoon representation with helices colored in red, sheets colored in yellow, and loops in green. (D) Two-step retaining mechanism of endoglucanase catalysis in (α/β)8 and β-jelly roll folds, where the configuration of the anomeric carbon is retained after hydrolysis and a glycosyl-enzyme intermediate is formed. (E) Single-step inverting mechanism of endoglucanase catalysis in (α/α)6 fold, where the configuration of the anomeric carbon is inverted; i.e hydrolysis of β-glycosidic bond leads to α-configuration of carbon and vice versa. In (α/β)8 and β-jelly roll fold, two glutamic acid residues act as the nucleophile and acid/base donor (shown in Inset (A) and Inset (B)). In (α/α)6 fold, a water molecule acts as the nucleophile, and glutamic acid and aspartic acid residues act as the acid/base donor (Inset (C)). The individual residues in stick representation are the nucleophile (in orange) and acid/base donor (in blue).