Α-Galactosidase

α-Galactosidase ( EC 3.2.1.22, α-GAL, α-GAL A; systematic name α-D-galactoside galactohydrolase) is a glycoside hydrolase enzyme that catalyses the hydrolysis of terminal, non-reducing α-D-galactose residues in α-D-galactosides, including galactooligosaccharides (GOS), galactomannans and galactolipids.

It catalyzes many catabolic processes, including cleavage of glycoproteins, glycolipids, and polysaccharides.

In humans, the enzyme is encoded by the GLA and MYORG genes.

The fungal Aspergillus niger aglA gene, originally annotated as an α‑galactosidase, actually encodes an enzyme with predominant α‑N‑acetylgalactosaminidase activity. This fungal "α‑galactosidase" is structurally and functionally most closely related to human α‑N‑acetylgalactosaminidase (NAGA, historically termed α‑galactosidase B), not to human α‑galactosidase A (GLA).

Structure

Human α‑galactosidases encoded by GLA and MYORG genes share a conserved modular architecture built around a TIM barrel catalytic domain with additional β‑sandwich accessory domains.

The lysosomal enzyme α‑galactosidase A (GLA product) is a secreted glycoprotein that forms a homodimer. Each subunit contains an N‑terminal TIM barrel harboring the active site and a C‑terminal antiparallel β‑sandwich, with multiple N‑linked glycans that stabilize the fold and mediate lysosomal targeting via mannose 6-phosphate receptors. In contrast, MYORG is a type I membrane glycoprotein located in the endoplasmic reticulum that also dimerizes and comprises an N‑terminal β‑sandwich‑like domain, a central TIM barrel catalytic domain, and a proximal β‑sheet domain, but it lacks the distal C‑terminal domain typical of other GH31 family members and instead uses an internal insertion region to form its dimer interface.

Function

This enzyme is a homodimeric glycoprotein that hydrolyses the terminal α-galactosyl moieties from glycolipids and glycoproteins.