Glucocerebrosidase
| Glucocerebrosidase | ||
|---|---|---|
|
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| Ribbon model of the GBA tetramer, according to PDB 3GXI | ||
|
Existing structure data: 1OGS , 1Y7V , 2F61 , 2J25 , 2NSX , 2NT0 , 2NT1 , 2V3D , 2V3E , 2V3F , 2VT0 , 2WCG , 2WKL , 2XWD , 2XWE , 3GXD , 3GXF , 3GXI , 3GXM , 3KE0 , 3KEH , 3rik , 3RIL |
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| Properties of human protein | ||
| Mass / length primary structure | 536 amino acids | |
| Cofactor | Saposin-C, anionic phospholipids | |
| Isoforms | 3 | |
| Identifier | ||
| Gene names | GBA GBA1; GCB; GLUC | |
| External IDs | ||
| Drug information | ||
| ATC code |
A16 AB01 A16 AB02 |
|
| DrugBank | DB00053 | |
| Enzyme classification | ||
| EC, category | 3.2.1.45 , glycosidase | |
| Response type | glycolytic cleavage | |
| Substrate | Glucocerebroside ( D- glucosyl- N -acylsphingosine), water | |
| Products | D - glucose and N -acylsphingosine | |
| Occurrence | ||
| Homology family | Glycosylceramidase | |
| Parent taxon | Creature | |
| Orthologue | ||
| human | House mouse | |
| Entrez | 2629 | 14466 |
| Ensemble | ENSG00000177628 | ENSMUSG00000028048 |
| UniProt | P04062 | P17439 |
| Refseq (mRNA) | NM_000157 | NM_001077411 |
| Refseq (protein) | NP_000148 | NP_001070879 |
| Gene locus | Chr 1: 155.23 - 155.24 Mb | Chr 3: 89.2 - 89.21 Mb |
| PubMed search | 2629 |
14466
|
Glucocerebrosidase (in German-speaking countries also glucocerebrosidase, chemically also glucosylceramidase ) is an enzyme that catalyzes the hydrolysis of the β- glucosidic bond of glucocerebroside ( D- glucosyl- N- acylsphingosine), an intermediate stage of the glycolipid metabolism. Glucosylceramidase is a lysosomal protein.
Mutations in the corresponding gene are the cause of Gaucher's disease , a lysosomal storage disease . The active ingredients derived from the enzyme alglucerase , velaglucerase and imiglucerase be administered as a substitute for this deficiency disease.
In the meantime, an increased risk of heterozygous carriers of glucocerebrosidase mutations for Parkinson's disease has also been observed. In particular, the disease occurs earlier than in the normal population. The accumulation of α-synuclein in the lysosomes that can be observed in Parkinson's disease is directly attributable to a glucosylceramidase deficiency.
Catalyzed reaction
+ H 2 O ⇒ 
+ glucose
Glucose is split off from β- D -glucosylceramide.
literature
- K. Brockmann, K. Srulijes et al. a .: GBA-associated PD presents with non-motor characteristics. In: Neurology. Volume 77, Number 3, July 2011, pp. 276-280, doi : 10.1212 / WNL.0b013e318225ab77 . PMID 21734182 .
- V. Cullen, SP Sardi, et al. a .: Acid β-glucosidase mutants linked to Gaucher disease, Parkinson disease, and Lewy body dementia alter α-synuclein processing. In: Annals of neurology . Volume 69, number 6, June 2011, pp. 940-953, doi : 10.1002 / ana.22400 . PMID 21472771 .
- S. Lesage, M. Anheim et al. a .: Large-scale screening of the Gaucher's disease-related glucocerebrosidase gene in Europeans with Parkinson's disease. In: Human molecular genetics . Volume 20, number 1, January 2011, pp. 202-210, doi : 10.1093 / hmg / ddq454 . PMID 20947659 .
Individual evidence
- ↑ Horowitz M, Zimran A: Mutations causing Gaucher disease. . In: Hum. Mutat. . 3, No. 1, 1994, pp. 1-11. doi : 10.1002 / humu.1380030102 . PMID 8118460 .
- ↑ Aharon-Peretz J, Rosenbaum H, Gershoni-Baruch R: Mutations in the glucocerebrosidase gene and Parkinson's disease in Ashkenazi Jews. N Engl J Med . 2004 Nov 4; 351 (19): 1972-7. PMID 15525722
- ^ TM Dawson, VL Dawson: A lysosomal lair for a pathogenic protein pair. In: Science Translational Medicine . Volume 3, number 91, July 2011, p. 91ps28, doi : 10.1126 / scitranslmed.3002808 . PMID 21753118 .
- ↑ JR Mazzulli, YH Xu et al. a .: Gaucher disease glucocerebrosidase and α-synuclein form a bidirectional pathogenic loop in synucleinopathies. In: Cell . Volume 146, Number 1, July 2011, pp. 37-52. doi : 10.1016 / j.cell.2011.06.001 . PMID 21700325 . PMC 3132082 (free full text).
Web links
- Proteopedia: Acid-β-glucosidase (Engl.)