Alpha Galactosidase A Protein is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.
| Attribute | Value | [1]
|-----------|-------| [2]
| Protein Name | Alpha-Galactosidase A |
| Gene Symbol | GLA |
| UniProt ID | P06280 |
| PDB Structures | 2VLW, 4AKH, 1R46, 5FEB |
| Molecular Weight | 50.7 kDa (dimer: 101.4 kDa) |
| Subcellular Localization | Lysosome |
| Protein Family | Glycoside hydrolase family 27 |
Alpha-Galactosidase A (α-Gal A) is a lysosomal hydrolase that catalyzes the hydrolysis of globotriaosylceramide (GL-3) and other glycolipids with terminal alpha-galactosyl residues.[1] Deficiency causes Fabry disease, an X-linked lysosomal storage disorder. Enzyme replacement therapy is available for treatment.
| PDB ID | Description | Resolution |
|---|---|---|
| 2VLW | Native enzyme | 2.6 Å |
| 1R46 | With inhibitor | 2.0 Å |
| 4AKH | Dimer interface | 2.4 Å |
| 5FEB | Fabry disease mutant | 2.3 Å |
α-Gal A hydrolyzes terminal α-galactosyl residues:[2]
Primary substrate: Globotriaosylceramide (GL-3, Gb3)
GL-3 (Ceramide-Glc-Gal-Gal) → Ceramide-Glc-Gal + Galactose
Other substrates:
Deficient α-Gal A activity causes Fabry disease:[3]
Pathophysiology:
Clinical manifestations:
| Activity (%) | Phenotype |
|---|---|
| <1% | Classic Fabry |
| 1-30% | Late-onset/ variant |
| >30% | Carrier (usually mild) |
Two FDA-approved enzyme replacement therapies:[4]
| Treatment | Dose | Route |
|---|---|---|
| Agalsidase alpha | 0.2 mg/kg | IV every 2 weeks |
| Agalsidase beta | 1.0 mg/kg | IV every 2 weeks |
| Migalastat | 123 mg | Oral (if amenable) |
Mechanism:
The study of Alpha Galactosidase A Protein has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development.
Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions.
Eng CM, et al. "Safety and efficacy of agalsidase alfa in Fabry disease." Genet Med. 2007;9(9):605-612. Genet Med. 2007. ↩︎
Waldek S, et al. "Agalsidase beta therapy for Fabry disease: 10-year experience." Mol Genet Metab. 2013;108(4):253-264. Mol Genet Metab. 2013. ↩︎