Alpha-galactosidase
| Galactosidase, alpha |
PDB rendering based on 1r46. |
| Available structures |
| PDB |
1R46, 1R47, 3GXN, 3GXP, 3GXT, 3HG2, 3HG3, 3HG4, 3HG5, 3LX9, 3LXA, 3LXB, 3LXC |
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| Identifiers |
| Symbols |
GLA; GALA |
| External IDs |
OMIM: 300644 MGI: 1347344 HomoloGene: 90852 GeneCards: GLA Gene |
| EC number |
3.2.1.22 |
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| RNA expression pattern |
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| More reference expression data |
| Orthologs |
| Species |
Human |
Mouse |
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| Entrez |
2717 |
11605 |
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| Ensembl |
ENSG00000102393 |
ENSMUSG00000031266 |
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| UniProt |
P06280 |
Q3TLY5 |
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| RefSeq (mRNA) |
NM_000169.2 |
NM_013463.2 |
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| RefSeq (protein) |
NP_000160.1 |
NP_038491.2 |
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| Location (UCSC) |
Chr X:
100.65 – 100.66 Mb |
Chr X:
131.12 – 131.14 Mb |
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| PubMed search |
[1] |
[2] |
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Alpha-galactosidase is a glycoside hydrolase enzyme that hydrolyses the terminal alpha-galactosyl moieties from glycolipids and glycoproteins. It is encoded by the GLA gene.[1]
Function
This enzyme is a homodimeric glycoprotein that hydrolyses the terminal alpha-galactosyl moieties from glycolipids and glycoproteins. It predominantly hydrolyzes ceramide trihexoside, and it can catalyze the hydrolysis of melibiose into galactose and glucose.
Pathology
A variety of mutations in this gene affect the synthesis, processing, and stability of this enzyme, which causes Fabry's disease, a rare lysosomal storage disorder and sphingolipidosis that results from a failure to catabolize alpha-D-galactosyl glycolipid moieties.[2]
Two enzyme replacement therapies are available to functionally compensate for alpha-galactosidase deficiency. Agalsidase alpha and beta are both recombinant forms of the human α-galactosidase A enzyme and both have the same amino acid sequence as the native enzyme. Agalsidase alpha and beta differ in the structures of their oligosaccharide side chains.[3]
Agalsidase alpha
The pharmaceutical company Shire manufactures agalsidase alpha under the brand name Replagal as a treatment for Fabry's disease.,[4] and was granted marketing approval in the EU in 2001.[5] As of 2010[update], FDA approval is still pending before the drug can be marketed in the United States.[6]
Agalsidase beta
The pharmaceutical company Genzyme produces synthetic agalsidase beta under the brand name Fabrazyme for treatment of Fabry's disease. In 2009, contamination at Genzyme's Allston, Massachusetts plant caused a worldwide shortage of Fabrazyme, and supplies were rationed to patients at one-third the recommended dose. Some patients have petitioned to break the company's patent on the drug under the "march-in" provisions of the Bayh–Dole Act.[6]
See also
References
Further reading
- Naumoff DG (2004). "Phylogenetic analysis of α-galactosidases of the GH27 family". Molecular Biology (Engl Transl) 38 (3): 388–399. PMID 15285616. PDF
- Eng CM, Desnick RJ (1994). "Molecular basis of Fabry disease: mutations and polymorphisms in the human alpha-galactosidase A gene.". Hum. Mutat. 3 (2): 103–11. doi:10.1002/humu.1380030204. PMID 7911050.
- Caillaud C, Poenaru L (2002). "[Gaucher's and Fabry's diseases: biochemical and genetic aspects]". J. Soc. Biol. 196 (2): 135–40. PMID 12360742.
- Germain DP (2002). "[Fabry's disease (alpha-galactosidase-A deficiency): physiopathology, clinical signs, and genetic aspects]". J. Soc. Biol. 196 (2): 161–73. PMID 12360745.
- Schaefer E, Mehta A, Gal A (2005). "Genotype and phenotype in Fabry disease: analysis of the Fabry Outcome Survey.". Acta paediatrica (Oslo, Norway : 1992). Supplement 94 (447): 87–92; discussion 79. doi:10.1080/08035320510031045. PMID 15895718.
- Levin M (2006). "Fabry disease.". Drugs Today 42 (1): 65–70. doi:10.1358/dot.2006.42.1.957357. PMID 16511611.
- Lidove O, Joly D, Barbey F, et al. (2007). "Clinical results of enzyme replacement therapy in Fabry disease: a comprehensive review of literature.". Int. J. Clin. Pract. 61 (2): 293–302. doi:10.1111/j.1742-1241.2006.01237.x. PMID 17263716.
- Dean KJ, Sweeley CC (1979). "Studies on human liver alpha-galactosidases. I. Purification of alpha-galactosidase A and its enzymatic properties with glycolipid and oligosaccharide substrates.". J. Biol. Chem. 254 (20): 9994–10000. PMID 39940.
- Ishii S, Sakuraba H, Suzuki Y (1992). "Point mutations in the upstream region of the alpha-galactosidase A gene exon 6 in an atypical variant of Fabry disease.". Hum. Genet. 89 (1): 29–32. doi:10.1007/BF00207037. PMID 1315715.
- Ioannou YA, Bishop DF, Desnick RJ (1992). "Overexpression of human alpha-galactosidase A results in its intracellular aggregation, crystallization in lysosomes, and selective secretion.". J. Cell Biol. 119 (5): 1137–50. doi:10.1083/jcb.119.5.1137. PMC 2289730. PMID 1332979. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2289730.
- von Scheidt W, Eng CM, Fitzmaurice TF, et al. (1991). "An atypical variant of Fabry's disease with manifestations confined to the myocardium.". N. Engl. J. Med. 324 (6): 395–9. doi:10.1056/NEJM199102073240607. PMID 1846223.
- Koide T, Ishiura M, Iwai K, et al. (1990). "A case of Fabry's disease in a patient with no alpha-galactosidase A activity caused by a single amino acid substitution of Pro-40 by Ser.". FEBS Lett. 259 (2): 353–6. doi:10.1016/0014-5793(90)80046-L. PMID 2152885.
- Kornreich R, Bishop DF, Desnick RJ (1990). "Alpha-galactosidase A gene rearrangements causing Fabry disease. Identification of short direct repeats at breakpoints in an Alu-rich gene.". J. Biol. Chem. 265 (16): 9319–26. PMID 2160973.
- Sakuraba H, Oshima A, Fukuhara Y, et al. (1990). "Identification of point mutations in the alpha-galactosidase A gene in classical and atypical hemizygotes with Fabry disease.". Am. J. Hum. Genet. 47 (5): 784–9. PMC 1683686. PMID 2171331. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1683686.
- Bernstein HS, Bishop DF, Astrin KH, et al. (1989). "Fabry disease: six gene rearrangements and an exonic point mutation in the alpha-galactosidase gene.". J. Clin. Invest. 83 (4): 1390–9. doi:10.1172/JCI114027. PMC 303833. PMID 2539398. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=303833.
- Kornreich R, Desnick RJ, Bishop DF (1989). "Nucleotide sequence of the human alpha-galactosidase A gene.". Nucleic Acids Res. 17 (8): 3301–2. doi:10.1093/nar/17.8.3301. PMC 317741. PMID 2542896. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=317741.
- Bishop DF, Kornreich R, Desnick RJ (1988). "Structural organization of the human alpha-galactosidase A gene: further evidence for the absence of a 3' untranslated region.". Proc. Natl. Acad. Sci. U.S.A. 85 (11): 3903–7. doi:10.1073/pnas.85.11.3903. PMC 280328. PMID 2836863. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=280328.
- Quinn M, Hantzopoulos P, Fidanza V, Calhoun DH (1988). "A genomic clone containing the promoter for the gene encoding the human lysosomal enzyme, alpha-galactosidase A.". Gene 58 (2-3): 177–88. doi:10.1016/0378-1119(87)90374-X. PMID 2892762.
- Bishop DF, Calhoun DH, Bernstein HS, et al. (1986). "Human alpha-galactosidase A: nucleotide sequence of a cDNA clone encoding the mature enzyme.". Proc. Natl. Acad. Sci. U.S.A. 83 (13): 4859–63. doi:10.1073/pnas.83.13.4859. PMC 323842. PMID 3014515. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=323842.
- Lemansky P, Bishop DF, Desnick RJ, et al. (1987). "Synthesis and processing of alpha-galactosidase A in human fibroblasts. Evidence for different mutations in Fabry disease.". J. Biol. Chem. 262 (5): 2062–5. PMID 3029062.
- Tsuji S, Martin BM, Kaslow DC, et al. (1987). "Signal sequence and DNA-mediated expression of human lysosomal alpha-galactosidase A.". Eur. J. Biochem. 165 (2): 275–80. doi:10.1111/j.1432-1033.1987.tb11438.x. PMID 3036505.
External links
This article incorporates text from the United States National Library of Medicine, which is in the public domain.
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PDB gallery
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1r46: Structure of human alpha-galactosidase
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1r47: Structure of human alpha-galactosidase
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| 3.2.1: Glycoside hydrolases |
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3.2.2: Hydrolysing
N-Glycosyl compounds |
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B enzm: 1.1/2/3/4/5/6/7/8/10/11/13/14/15-18, 2.1/2/3/4/5/6/7/8, 2.7.10, 2.7.11-12, 3.1/2/3/4/5/6/7, 3.1.3.48, 3.4.21/22/23/24, 4.1/2/3/4/5/6, 5.1/2/3/4/99, 6.1-3/4/5-6
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| Sphingolipid |
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| NCL |
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| Ceramide synthesis |
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mt, k, c/g/r/p/y/i, f/h/s/l/o/e, a/u, n, m
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k, cgrp/y/i, f/h/s/l/o/e, au, n, m, epon
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m(A16/C10),i(k, c/g/r/p/y/i, f/h/s/o/e, a/u, n, m)
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