This domain contains two disulfide bridges that are necessary for correct folding, as well as a glycosylated residue (Asn19) that is required for catalytic activity in vivo.

[8] Domain III harbors the active site, which binds the substrate glucocerebroside in close proximity to the catalytic residues E340 and E235.

[7] Crystal structures indicate that β-glucocerebrosidase binds the glucose moiety and adjacent O-glycosydic bond of glucocerebroside.

The two aliphatic chains of glucocerebroside may remain associated with the lysosomal bilayer or interact with the activating protein Saposin C.[7] Consistent with other glycoside hydrolases, the mechanism of glucocerebroside hydrolysis by β-glucocerebrosidase involves acid/base catalysis by two glutamic acid residues (E340 and E235) and precedes through a two-step mechanism.

In the first step, E340 performs a nucleophilic attack at the carbon of the O-glycosidic linkage to displace the sphingosine moiety, which is simultaneously protonated by E235 as it is released from the active site.

Drugs made recombinantly pose no risk of diseases being transmitted from the tissue used in harvesting, and are less expensive to manufacture.